Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease
Abstract
:1. Introduction
2. Vascular-Neurovascular Hypothesis: Microvessel Remodeling and Cerebral Small Vessel Disease (SVD) Contributions to Neurodegeneration
2.1. Neurovascular Unit Brain Endothelial Cells and Brain Endothelial Cell Activation and Dysfunction (BECact/dys)
2.2. Neurovascular Unit Pericyte (Pc) Remodeling
2.3. Brief Overview of Neurovascular Unit (NVU) Reactive Perivascular Astrocyte(s) (rpvACs) and Reactive Microglia Cells (rMGCs) That Contribute to Neurodegeneration (ND)
3. Neural Oxidative Redox Stress (OxRS) Including: ROS, Reactive Oxygen, Nitrogen, Sulfur Species (RONSS), and Iron Sulfur Clusters (ISCs) of the Reactive Species Interactome (RSI)
4. Neuroinflammation and Neurodegeneration
5. Neurodegeneration
6. Cerebral Amyloid Angiopathy (CAA) Role in the Development and Progression of LOAD
7. Conclusions
8. Future Directions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Shulyatnikova, T.; Hayden, M.R. Why Are Perivascular Spaces Important? Medicina 2023, 59, 917. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R. A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Biomedicines 2024, 12, 96. [Google Scholar] [CrossRef] [PubMed]
- Iturria-Medina, Y.; Sotero, R.C.; Toussaint, P.J.; Mateos-Pérez, J.M.; Evans, A.C. Alzheimer’s Disease Neuroimaging Initiative. Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat. Commun. 2016, 7, 11934. [Google Scholar] [CrossRef] [PubMed]
- Iadecola, C. The Pathobiology of Vascular Dementia. Neuron 2013, 80, 844–866. [Google Scholar] [CrossRef] [PubMed]
- Liu, P.P.; Xie, Y.; Meng, X.Y.; Kang, J.S. History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct Target Ther. 2019, 4, 29. [Google Scholar] [CrossRef]
- Hayden, M.R. Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy. Brain Sci. 2019, 9, 262. [Google Scholar] [CrossRef]
- Du, X.; Wang, X.; Geng, M. Alzheimer’s disease hypothesis and related therapies. Transl. Neurodegener. 2018, 7, 2. [Google Scholar] [CrossRef]
- Hardy, J.; Allsop, D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol. Sci. 1991, 12, 383–388. [Google Scholar] [CrossRef]
- Selkoe, D.J. The molecular pathology of Alzheimer’s disease. Neuron 1991, 6, 487–498. [Google Scholar] [CrossRef]
- Swerdlow, R.H.; Khan, S.M. A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med. Hypotheses. 2004, 63, 8–20. [Google Scholar] [CrossRef]
- Musiek, E.S.; Holtzman, D.M. Three Dimensions of the Amyloid Hypothesis: Time, Space, and “Wingmen”. Nat. Neurosci. 2015, 18, 800–806. [Google Scholar] [CrossRef] [PubMed]
- Jacob, M.A.; Cai, M.; van de Donk, V.; Bergkamp, M.; Marques, J.; Norris, D.G.; Kessels, R.P.C.; Jurgen, A.H.R.; Duering, M.; Tuladhar, A.M.; et al. Cerebral Small Vessel Disease Progression and the Risk of Dementia: A 14-Year Follow-Up Study. Am. J. Psychiatry. 2023, 180, 508–518. [Google Scholar] [CrossRef] [PubMed]
- NIH: National Institute of Neurological Disorders and Stroke. The MarkVCID Consortium Overview. Available online: https://www.ninds.nih.gov (accessed on 25 October 2024).
- Wardlaw, J.M.; Smith, C.; Dichgans, M. Small vessel disease: Mechanisms and clinical implications. Lancet Neurol. 2019, 18, 684–696. [Google Scholar] [CrossRef] [PubMed]
- Paoletti, F.P.; Simoni, S.; Parnetti, L.; Gaetani, L. The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease, Parkinson’s Disease and Multiple Sclerosis. Int. J. Mol. Sci. 2021, 22, 4958. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R. Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Neuroglia 2023, 4, 307–328. [Google Scholar] [CrossRef]
- Verkhratsky, A.; Butt, A.M. Neuroglia: Function and Pathology, 1st ed.; Academic Press: London, UK, 2023. [Google Scholar]
- Verkhratsky, A.; Nedergaard, M. Astroglial cradle in the life of the synapse. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2014, 369, 20130595. [Google Scholar] [CrossRef]
- Verkhratsky, A.; Nedergaard, M. Physiology of Astroglia. Physiol. Rev. 2018, 98, 239–389. [Google Scholar] [CrossRef]
- Verkhratsky, A.; Parpura, V.; Li, B.; Sucder, C. Astrocytes: The housekeepers of the CNS. Adv. Neurobiol. 2021, 26, 21–53. [Google Scholar] [CrossRef]
- Hayden, M.R. Hypothesis: Astrocyte Foot Processes Detachment from the Neurovascular Unit in Female Diabetic Mice May Impair Modulation of Information Processing—Six Degrees of Separation. Brain Sci. 2019, 9, 83. [Google Scholar] [CrossRef]
- de la Torre, J.C. Alzheimer disease as a vascular disorder: Nosological evidence. Stroke 2002, 33, 1152–1162. [Google Scholar] [CrossRef]
- Zlokovic, B.V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci. 2011, 12, 723–738. [Google Scholar] [CrossRef] [PubMed]
- Toledo, J.B.; Arnold, S.E.; Raible, K.; Brettschneider, J.; Xie, S.X.; Grossman, M.; Trojanowski, J.Q. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 2013, 136 Pt 9, 2697–2706. [Google Scholar] [CrossRef] [PubMed]
- Avelar-Pereira, B.; Belloy, M.E.; O’Hara, R.; Hadi Hosseini, S.M. Decoding the heterogeneity of Alzheimer’s disease diagnosis and progression using multilayer networks. Mol. Psychiatry 2023, 28, 2423–2432. [Google Scholar] [CrossRef] [PubMed]
- Jellinger, A. Basic mechanisms of neurodegeneration: A critical update. J. Cell Mol. Med. 2010, 14, 457–487. [Google Scholar] [CrossRef] [PubMed]
- Sweeney, M.D.; Montagne, A.; Sagare, A.P.; Nation, D.A.; Schneider, L.S.; Chui, H.C.; Harrington, M.G.; Pa, J.; Law, M.; Wang, D.J.J.; et al. Vascular dysfunction-The disregarded partner of Alzheimer’s disease. Alzheimer’s Dement. 2019, 15, 158–167. [Google Scholar] [CrossRef] [PubMed]
- de la Torre, J.C. Cerebromicrovascular pathology in Alzheimer’s disease compared to normal aging. Gerontology 1997, 43, 26–43. [Google Scholar] [CrossRef]
- O’Brien, J.T.; Markus, H.S. Vascular risk factors and Alzheimer’s disease. BMC Med. 2014, 12, 218. [Google Scholar] [CrossRef]
- Grammas, P. Neurovascular dysfunction, inflammation and endothelial activation: Implications for the pathogenesis of Alzheimer’s disease. J. Neuroinflamm. 2011, 8, 26. [Google Scholar] [CrossRef]
- Tarawneh, R. Microvascular Contributions to Alzheimer Disease Pathogenesis: Is Alzheimer Disease Primarily an Endotheliopathy? Biomolecules 2023, 13, 830. [Google Scholar] [CrossRef]
- de la Torre, J.C. Is Alzheimer’s disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol. 2004, 3, 184–190. [Google Scholar] [CrossRef]
- Rizvi, B.; Lao, P.J.; Chesebro, A.G.; Dworkin, J.D.; Amarante, E.; Beato, J.M.; Gutierrez, J.; West, L.B.; Schupf, N.; Manly, J.J.; et al. Association of Regional White Matter Hyperintensities with Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults. JAMA Netw. Open. 2021, 4, e2125166. [Google Scholar] [CrossRef] [PubMed]
- Montagne, A.; Barnes, S.R.; Sweeney, M.D.; Halliday, M.R.; Sagare, A.P.; Zhao, Z.; Toga, A.W.; Jacobs, R.E.; Liu, C.Y.; Amezcua, L. Blood-Brain Barrier Breakdown in the Aging Human Hippocampus. Neuron 2015, 85, 296–302. [Google Scholar] [CrossRef] [PubMed]
- Gyanwali, B.; Shaik, M.A.; Tan, C.S.; Vrooman, H.; Venketasubramanian, N.; Chen, C.; Hilal, S. Mixed-location cerebral microbleeds as a biomarker of neurodegeneration in a memory clinic population. Aging 2019, 11, 10581–10596. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R. Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood–Brain Barrier Dysfunction/Disruption with Increased Risk of Hemorrhagic and Ischemic Stroke. Biomedicines 2024, 12, 1463. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R. Brain Injury: Response to Injury Wound-Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Medicina 2023, 59, 1337. [Google Scholar] [CrossRef]
- Han, F. Cerebral microvascular dysfunction and neurodegeneration in dementia. Stroke Vasc. Neurol. 2019, 4, 105–107. [Google Scholar] [CrossRef]
- Hayden, M.R. Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome. Medicina 2023, 59, 1124. [Google Scholar] [CrossRef]
- Hayden, M.R. Brain endothelial cell activation and dysfunction associate with and contribute to the development of enlarged perivascular spaces and cerebral small vessel disease. Histol Histopathol. 2024, 35, 1565–1586. [Google Scholar] [CrossRef]
- Hayden, M.R.; Grant, D.G.; Aroor, A.R.; DeMarco, V.G. Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part I: Astrocyte. Neuroglia 2018, 1, 220–244. [Google Scholar] [CrossRef]
- Hayden, M.R. The Brain Endothelial Cell Glycocalyx Plays a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Life 2023, 13, 1955. [Google Scholar] [CrossRef]
- Salameh, T.S.; Shah, G.N.; Price, T.O.; Hayden, M.R.; Banks, W.A. Blood-Brain Barrier Disruption and Neurovascular Unit Dysfunction in Diabetic Mice: Protection with the Mitochondrial Carbonic Anhydrase Inhibitor Topiramate. J. Pharmacol. Exp. Ther. 2016, 359, 452–459. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R.; Yang, Y.; Habibi, J.; Bagree, S.V.; Sowers, J.R. Pericytopathy: Oxidative stress and impaired cellular longevity in the pancreas and skeletal muscle in metabolic syndrome and type 2 diabetes. Oxid. Med. Cell Longev. 2010, 3, 290–303. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R. Pericytes and Perivascular Macrophages Play a Key Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome and Type 2 Diabetes Mellitus. J. Alzheimers Neurodegener. Diseases 2023, 9, 62. [Google Scholar] [CrossRef] [PubMed]
- Winkler, E.A.; Sagare, A.P.; Zlokovic, B.V. The Pericyte: A Forgotten Cell Type with Important Implications for Alzheimer’s Disease? Brain Pathol. 2014, 24, 371–386. [Google Scholar] [CrossRef]
- Sweeney, M.D.; Ayyadurai, S.; Zlokovic, B.V. Pericytes of the neurovascular unit: Key functions and signaling pathways. Nat. Neurosci. 2016, 19, 771–783. [Google Scholar] [CrossRef]
- Allt, G.; Lawrenson, J.G. Pericytes: Cell biology and pathology. Cells Tissues Organs 2001, 169, 1–11. [Google Scholar] [CrossRef]
- Bell, R.D.; Winkler, E.A.; Sagare, A.P.; Singh, I.; LaRue, B.; Deane, R.; Zlokovic, B.V. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 2010, 68, 409–427. [Google Scholar] [CrossRef]
- Armulik, A.; Genove, G.; Betsholtz, C. Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 2011, 21, 193–215. [Google Scholar] [CrossRef]
- Attwell, D.; Mishra, A.; Hall, C.N.; O’Farrell, F.M.; Dalkara, T. What is a pericyte? J. Cereb. Blood Flow Metab. 2016, 36, 451–455. [Google Scholar] [CrossRef]
- Uemura Mt Maki, T.; Ihara, M.; Lee, V.M.Y.; Trojanowski, J.Q. Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia. Front. Aging Neurosci. 2020, 12, 80. [Google Scholar] [CrossRef]
- Hall, C.N.; Reynell, C.; Gesslein, B.; Hamilton, N.B.; Mishra, A.; Sutherland, B.A.; O’Farrell, F.M.; Buchan, A.M.; Lauritzen, M.; Attwell, D. Capillary pericytes regulate cerebral blood flow in health and disease. Nature 2014, 508, 55–60. [Google Scholar] [CrossRef] [PubMed]
- Cai, W.; Liu, H.; Zhao, J.; Chen, L.Y.; Chen, J.; Zhengqi Lu Hu, X. Pericytes in brain injury and repair after ischemic stroke. Transl. Stroke Res. 2017, 8, 107–121. [Google Scholar] [CrossRef] [PubMed]
- Korte, N.; Nortley, R.; Attwell, D. Cerebral blood flow decrease as an early pathological mechanism in Alzheimer’s disease. Acta Neuropathol. 2020, 140, 793–810. [Google Scholar] [CrossRef] [PubMed]
- Dore-Duffy, P.; Katychev, A.; Wang, X.; Van Buren, E. CNS microvascular pericytes exhibit multipotential stem cell activity. J. Cereb. Blood Flow Metab. 2006, 26, 613–624. [Google Scholar] [CrossRef]
- Darden, J.; Payne, L.B.; Zhao, H.; Chappell, J.C. Excess Vascular Endothelial Growth Factor-A Disrupts Pericyte Recruitment during Blood Vessel Formation. Angiogenesis 2019, 22, 167–183. [Google Scholar] [CrossRef]
- Li, X.; Lee, C.; Tang, Z.; Zhang, F.; Arjunan, P.; Li, Y.; Hou, X.; Kumar, A.; Dong, L. VEGF-B: A survival, or an angiogenic factor? Cell Adh. Migr. 2009, 3, 322–327. [Google Scholar] [CrossRef]
- Erickson, M.A.; Shulyatnikova, T.; Banks WAHayden, M.R. Ultrastructural Remodeling of the Blood-Brain Barrier and Neurovascular Unit by Lipopolysaccharide-Induced Neuroinflammation. Int. J. Mol. Sci. 2023, 24, 1640. [Google Scholar] [CrossRef]
- Hayden, M.R.; Grant, D.G.; Aroor, A.R.; DeMarco, V.G. Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model–Part II: Microglia and Mitochondria. Neuroglia 2018, 1, 311–326. [Google Scholar] [CrossRef]
- Hayden, M.R. The Mighty Mitochondria Are Unifying Organelles and Metabolic Hubs in Multiple Organs of Obesity, Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes: An Observational Ultrastructure Study. Int. J. Mol. Sci. 2022, 23, 4820. [Google Scholar] [CrossRef]
- Nortley, R.; Korte, N.; Izquierdo, P.; Hirunpattarasilp, C.; Mishra, A.; Jaunmuktane, Z.; Kyrargyri, V.; Pfeiffer, T.; Khennouf, L.; Madry, C. Amyloid β oligomers constrict human capillaries in Alzheimer’s disease via signaling to pericytes. Science 2019, 365, eaav9518. [Google Scholar] [CrossRef]
- Armulik, A.; Abramsson, A.; Betsholtz, C. Endothelial/pericyte interactions. Circ. Res. 2005, 97, 512–523. [Google Scholar] [CrossRef] [PubMed]
- Cheng, J.; Korte, N.; Nortley, R.; Sethi, H.; Tang, Y.; Attwell, D. Targeting pericytes for therapeutic approaches to neurological disorders. Acta Neuropathol. 2018, 136, 507–523. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.; Guo, D.; Zhu, Y.; Xiao, S.; Xie, J.; Zhang, Z.; Hu, Y.; Huang, J.; Ma, X.; Ning, Z. Amyloid β oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction. Alzheimers Res. Ther. 2024, 16, 56. [Google Scholar] [CrossRef]
- Duenas, M.; Luquin, S.; Chowen, J.A.; Torres-Aleman, I.; Naftolin, F.; Garcia-Segura, L.M. Gonadal hormone regulation of insulin-like growth factor-I-like immunoreactivity in hypothalamic astroglia of developing and adult rats. Neuroendocrinology 1994, 59, 528–538. [Google Scholar] [CrossRef]
- Buchanan, C.D.; Mahesh, V.B.; Brann, D.W. Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling: A role for transforming growth factor-beta (1). Biol. Reprod. 2000, 62, 1710–1721. [Google Scholar] [CrossRef] [PubMed]
- Flores, C.; Salmaso, N.; Cain, S.; Rodaros, D.; Stewart, J. Ovariectomy of adult rats leads to increased expression of astrocytic basic fibroblast growth factor in the ventral tegmental area and in dopaminergic projection regions of the entorhinal and prefrontal cortex. J. Neurosci. 1999, 19, 8665–8673. [Google Scholar] [CrossRef] [PubMed]
- Karki, P.; Smith, K.; Johnson, J., Jr.; Lee, E. Astrocyte-derived growth factors and estrogen neuroprotection: Role of transforming growth factor-α in estrogen-induced upregulation of glutamate transporters in astrocytes. Mol. Cell Endocrinol. 2014, 389, 58–64. [Google Scholar] [CrossRef]
- Owens, T.; Bechmann, I.; Engelhardt, B. Perivascular Spaces and the Two Steps to Neuroinflammation. J. Neuropathol. Exp. Neurol. 2008, 67, 1113–1121. [Google Scholar] [CrossRef]
- Trolli, F.; Cipollini, V.; Moci, M.; Morena, E.; Palotai, M.; Rinaldi, V.; Romano, C.; Ristori, G.; Giubilei, F.; Salvetti, M.; et al. Perivascular Unit: This Must Be the Place. The Anatomical Crossroad Between the Immune Vascular and Nervous System. Front. Neuroanat. 2020, 14, 17. [Google Scholar] [CrossRef]
- Kisler, K.; Nelson, A.R.; Montagne, A.; Zlokovic, B.V. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer’s disease. Nat. Rev. Neurosci. 2017, 18, 419–434. [Google Scholar] [CrossRef]
- Verkratsky, A.; Olabarria, M.; Noristani, H.N.; Yeh, C.Y.; Rodriguez, J.J. Astrocytes in Alzheimer’s Disease. Neurotherapeutics 2010, 7, 399–412. [Google Scholar] [CrossRef] [PubMed]
- Walker, L.C. Aβ plaques. Free Neuropathol. 2020, 1, 31. [Google Scholar] [CrossRef] [PubMed]
- Shulyatnikova, T.; Verkhratsky, A. Astroglia in Sepsis Associated Encephalopathy. Neurochem. Res. 2020, 45, 83–99. [Google Scholar] [CrossRef]
- Tolar, M.; Hey, J.; Power, A.; Abushakra, S. Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression. Int. J. Mol. Sci. 2021, 22, 6355. [Google Scholar] [CrossRef] [PubMed]
- Zlokovic, B.V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008, 57, 178–201. [Google Scholar] [CrossRef] [PubMed]
- Rabinovici, G.D. Late-onset Alzheimer Disease. Continuum 2019, 25, 14–33. [Google Scholar] [CrossRef]
- Hayden, M.R.; Tyagi, S.C. Intimal redox stress: Accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscler. Cardiovasc. Diabetol. 2002, 1, 3. [Google Scholar] [CrossRef]
- Butterfield, D.A.; Perluigi, M.; Sultana, R. Oxidative stress in Alzheimer’s disease brain: New insights from redox proteomics. Eur. J. Pharmacol. 2006, 545, 39–50. [Google Scholar] [CrossRef]
- Sbodio, J.I.; Snyder, S.H.; Bindu, D.P. Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities. Antioxid. Redox Signal. 2019, 30, 1450–1499. [Google Scholar] [CrossRef]
- Shi, R.; Hou, W.; Wang, Z.Q.; Xu, X. Biogenesis of Iron–Sulfur Clusters and Their Role in DNA Metabolism. Front. Cell Dev. Biol. 2021, 9, 735678. [Google Scholar] [CrossRef]
- Isaya, G. Mitochondrial iron-sulfur cluster dysfunction in neurodegenerative disease. Front. Pharmacol. 2014, 5, 29. [Google Scholar] [CrossRef] [PubMed]
- Selvanathan, A.; Sankaran, B.P. Mitochondrial iron-sulfur cluster biogenesis and neurological disorders. Mitochondrion 2022, 62, 41–49. [Google Scholar] [CrossRef] [PubMed]
- Hayden, M.R. Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease. Medicina 2023, 59, 561. [Google Scholar] [CrossRef] [PubMed]
- Kiraly, M.; Foss, J.F.; Giordano, T. Neuroinflammation, Its Role in Alzheimer’s Disease and Therapeutic strategies. J. Prev. Alzheimers Dis. 2023, 10, 686–698. [Google Scholar] [CrossRef] [PubMed]
- Thakur, S.; Dhapola, R.; Sarma, P.; Medhi, B.; Reddy, D.H. Neuroinflammation in Alzheimer’s Disease: Current Progress in Molecular Signaling and Therapeutics. Inflammation 2023, 46, 1–17. [Google Scholar] [CrossRef]
- Ashford, J.W. APOE genotype effects on Alzheimer’s disease onset and epidemiology. J. Mol. Neurosci. 2004, 23, 157–165. [Google Scholar] [CrossRef]
- Crews, L.; Masliah, E. Molecular mechanisms of neurodegeneration in Alzheimer’s disease. Hum. Mol. Genet. 2010, 19, R12–R20. [Google Scholar] [CrossRef]
- Katzman, R. Alzheimer’s disease. N. Engl. J. Med. 1986, 314, 964–973. [Google Scholar] [CrossRef]
- Budson, A.E.; Price, B.H. Memory dysfunction. N. Engl. J. Med. 2005, 352, 692–699. [Google Scholar] [CrossRef]
- Masliah, E.; Mallory, M.; Alford, M.; DeTeresa, R.; Iwai, A.; Saitoh, T. Molecular mechanisms of synaptic disconnection in Alzheimer’s disease. In Connections, Cognition and Alzheimer’s Disease; Hyman, B., Duyckaerts, C., Christen, Y., Eds.; Springer: Berlin, Germany, 1997; pp. 121–140. [Google Scholar]
- DeKosky, S.; Scheff, S. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: Correlation with cognitive severity. Ann. Neurol. 1990, 27, 457–464. [Google Scholar] [CrossRef]
- Terry, R.; Peck, A.; DeTeresa, R.; Schechter, R.; Horoupian, D. Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann. Neurol. 1981, 10, 184–192. [Google Scholar] [CrossRef] [PubMed]
- Beach, T.; Walker, R.; McGeer, E. Patterns of gliosis in Alzheimer’s disease and aging cerebrum. Glia 1989, 2, 420–436. [Google Scholar] [CrossRef] [PubMed]
- Rogers, J.; Luber-Narod, J.; Styren, S.; Civin, W. Expression of immune system-associated antigens by cells of the human central nervous system: Relationship to the pathology of Alzheimer’s disease. Neurobiol. Aging 1988, 9, 339–349. [Google Scholar] [CrossRef] [PubMed]
- Masliah, E.; Mallory, M.; Hansen, L.; Alford, M.; Albright, T.; Terry, R.; Shapiro, P.; Sundsmo, M.; Saitoh, T. Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in Alzheimer disease. Acta Neuropathol. 1991, 83, 12–20. [Google Scholar] [CrossRef] [PubMed]
- Trojanowski, J.Q.; Lee, V.M. ‘Fatal attractions’ of proteins. A comprehensive hypothetical mechanism underlying Alzheimer’s disease and other neurodegenerative disorders. Ann. N. Y. Acad. Sci. 2000, 924, 62–67. [Google Scholar] [CrossRef]
- Lee, V.M.; Goedert, M.; Trojanowski, J.Q. Neurodegenerative tauopathies. Ann. Rev. Neurosci. 2001, 24, 1121–1159. [Google Scholar] [CrossRef]
- Iqbal, K.; Grundke-Iqbal, I. Neurofibrillary pathology leads to synaptic loss and not the other way around in Alzheimer disease. J. Alzheimers Dis. 2002, 4, 235–238. [Google Scholar] [CrossRef]
- Mandelkow, E.M.; Mandelkow, E. Tau in Alzheimer’s disease. Trends Cell Biol. 1998, 8, 425–427. [Google Scholar] [CrossRef]
- Crews, L.; Rockenstein, E.; Masliah, E. APP transgenic modeling of Alzheimer’s disease: Mechanisms of neurodegeneration and aberrant neurogenesis. Brain Struct. Funct. 2010, 214, 111–126. [Google Scholar] [CrossRef]
- Gorman, A.M. Neuronal cell death in neurodegenerative diseases: Recurring themes around protein handling. J. Cell Mol. Med. 2008, 12, 2263–2280. [Google Scholar] [CrossRef]
- Padurariu, M.; Ciobica, A.; Lefter, R.; Serban, I.L.; Stefanescu, C.; Chirita, R. The oxidative stress hypothesis in Alzheimer’s disease. Psychiatria Danubina 2013, 25, 401–409. [Google Scholar] [PubMed]
- Xie, A.; Gao, J.; Xu, L.; Meng, D. Shared Mechanisms of Neurodegeneration in Alzheimer’s Disease and Parkinson’s Disease. BioMed Res. Int. 2014, 2014, 648740. [Google Scholar] [CrossRef] [PubMed]
- Iwata, N.; Tsubuki, S.; Takaki, Y.; Shirotani, K.; Lu, B.; Gerard, N.P.; Gerard, C.; Hama, E.; Lee, H.J.; Saido, T.C. Metabolic regulation of brain Abeta by neprilysin. Science 2001, 292, 1550–1552. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Basak, J.M.; Holtzman, D.M. The role of apolipoprotein E in Alzheimer’s disease. Neuron 2009, 63, 287–303. [Google Scholar] [CrossRef]
- Bendiske, J.; Bahr, B.A. Lysosomal activation is a compensatory response against protein accumulation and associated synaptopathogenesis—An approach for slowing Alzheimer disease? J. Neuropathol. Exp. Neurol. 2003, 62, 451–463. [Google Scholar] [CrossRef]
- Marambaud, P.; Zhao, H.; Davies, P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J. Biol. Chem. 2005, 280, 37377–37382. [Google Scholar] [CrossRef]
- Walsh, D.M.; Selkoe, D.J. Oligomers on the brain: The emerging role of soluble protein aggregates in neurodegeneration. Protein Pept. Lett. 2004, 11, 213–228. [Google Scholar] [CrossRef]
- Klein, W.L.; Krafft, G.A.; Finch, C.E. Targeting small Abeta oligomers: The solution to an Alzheimer’s disease conundrum? Trends Neurosci. 2001, 24, 219–224. [Google Scholar] [CrossRef]
- McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R., Jr.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011, 7, 263–269. [Google Scholar] [CrossRef]
- Jack, C.R., Jr.; Petersen, R.C.; Xu, Y.C.; Waring, S.C.; O’Brien, P.C.; Tangalos, E.G.; Smith, G.E.; Ivnik, R.J.; Kokmen, E. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology 1997, 49, 786–794. [Google Scholar] [CrossRef]
- Banks, W.A.; Hayden, M.R. Deficient Leptin Cellular Signaling Plays a Key Role in Brain Ultrastructural Remodeling in Obesity and Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2021, 22, 5427. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Rodriguez, J.J.; Ortiz, O.; Jimenez-Palomares, M.; Kay, K.R.; Berrocoso, E.; Murillo-Carretero, M.I.; Perdomo, G.; Spires-Jones, T.; Cozar-Castellano, I.; Lechuga-Sancho, A.M.; et al. Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice. Psychoneuroendocrinology 2013, 38, 2462–2475. [Google Scholar] [CrossRef] [PubMed]
- Meftah, S.; Gan, J. Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Front. Synaptic Neurosci. 2023, 15, 1129036. [Google Scholar] [CrossRef] [PubMed]
- Selkoe, D.J. Alzheimer’s disease is a synaptic failure. Science. 2002, 298, 789–791. [Google Scholar] [CrossRef] [PubMed]
- Jackson, J.; Jambrina, E.; Li, J.; Marston, H.; Menzies, F.; Phillips, K.; Perdomo, G.; Spiers-Jones, T.; Cozar-Castellano, I.; Lechuga-Sancho, A.M.; et al. Targeting the Synapse in Alzheimer’s Disease. Front. Neurosci. 2019, 13, 735. [Google Scholar] [CrossRef]
- Schirinzi, T.; Canevelli, M.; Suppa, A.; Bologna, M.; Marsili, L. The continuum between neurodegeneration, brain plasticity, and movement: A critical appraisal. Rev. Neurosci. 2020, 31, 723–742. [Google Scholar] [CrossRef]
- Qi, X.M.; Ma, J.F. The role of amyloid beta clearance in cerebral amyloid angiopathy: More potential therapeutic targets. Trans. Neurodegener 2017, 6, 22. [Google Scholar] [CrossRef]
- Wang, L.; Liu, Q.; Yue, D.; Liu, J.; Fu, Y. Cerebral Amyloid Angiopathy: An Undeniable Small Vessel Disease. J. Stroke 2024, 26, 1–12. [Google Scholar] [CrossRef]
- Greenberg, S.M.; Bacskai, B.J.; Hernandez-Guillamon, M.; Pruzin, J.; Sperling, R.; vanVeluw, S.J. Cerebral amyloid angiopathy and Alzheimer disease—One peptide, two pathways. Nat. Rev. Neurol. 2019, 16, 30–42. [Google Scholar] [CrossRef]
- Greenberg, S.M.; Charidimou, A. Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria. Stroke 2018, 49, 491–497. [Google Scholar] [CrossRef]
- Ghiso, J.; Tomidokoro, Y.; Revesz, T.; Frangione, B.; Rostagno, A. Cerebral amyloid angiopathy and Alzheimer’s disease. Hirosaki Igaku 2010, 61, S111–S124. [Google Scholar] [PubMed]
- Alzheimer, A.; Stelzmann, R.A.; Schnitzlein, H.N.; Murtagh, F.R. An English translation of Alzheimer’s 1907 paper, Uber eine eigenartige Erkankung der Hirnrinde. Clin. Anat. 1995, 8, 429–431. [Google Scholar] [CrossRef] [PubMed]
- Alzheimer, A.; Förstl, H.; Levy, R. On certain peculiar diseases of old age. Hist. Psychiatry 1991, 2 Pt 1, 71–101. [Google Scholar] [CrossRef] [PubMed]
- Alzheimer, A. A contribution concerning the pathological anatomy of mental disturbances in old age. Alzheimer Dis. Assoc. Disord. 1991, 5, 69–70. [Google Scholar]
- Berry, C.; Sidik, N.; Pereira, A.C.; Ford, T.J.; Touyz, R.M.; Kaski, J.C.; Hainsworth, A.H. Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions. J. Am. Heart Assoc. 2019, 8, e011104. [Google Scholar] [CrossRef]
- Corriveau, R.A.; Bosetti, F.; Emr, M.; Gladman, J.T.; Koenig, J.I.; Moy, C.S.; Pahigiannis, K.; Waddy, S.P.; Koroshetz, W. The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline. Cell. Mol. Neurobiol. 2016, 36, 281–288. [Google Scholar] [CrossRef]
- Zlokovic, B.V.; Griffin, J.H. Cytoprotective protein C pathways and implications for stroke and neurological disorders. Trends Neurosci. 2011, 34, 198–209. [Google Scholar] [CrossRef]
- Ter Telgte, A.; van Leijsen, E.M.C.; Wiegertjes, K.; Klijn, C.J.M.; Tuladhar, A.M.; de Leeuw, F.E. Cerebral small vessel disease: From a focal to a global perspective. Nat. Rev. Neurol. 2018, 14, 387–398. [Google Scholar] [CrossRef]
- Fischer, M.; Garcia, J.H. The Ischemic Penumbra: Identification, Evolution and Treatment Concepts. Cerebrovasc. Dis. 2004, 17 (Suppl. 1), 1–6. [Google Scholar] [CrossRef]
- Liu, S.; Levine, S.R.; Winn, H.R. Targeting ischemic penumbra: Part I—From pathophysiology to therapeutic strategy. Exp. Stroke Transl. Med. 2010, 3, 47–55. [Google Scholar] [CrossRef]
- Grammas, P.; Moore, P.; Weigel, P.H. Microvessels from Alzheimer’s Disease Brains Kill Neurons In Vitro. Am. J. Pathol. 1999, 154, 337–342. [Google Scholar] [CrossRef] [PubMed]
- Markus, H.S.; de Leeuw, F.E. Cerebral small vessel disease: Recent advances and future directions. Int. J. Stroke 2023, 18, 4–14. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.W.; Hong, J.; Jeon, J.C. Cerebral Small Vessel Disease and Alzheimer’s Disease: A Review. Front. Neurol. 2020, 11, 927. [Google Scholar] [CrossRef] [PubMed]
- Nyúl-Tóth, Á.; Patai, R.; Csiszar, A.; Ungvari, A.; Gulej, R.; Mukli, P.; Yabluchansky, A.; Bene, Z.; Sotonii, P.; Sold, K.I.; et al. Linking peripheral atherosclerosis to blood–brain barrier disruption: Elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment. GeroScience 2024, 46, 6511–6536. [Google Scholar] [CrossRef]
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Hayden, M.R. Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease. J. Vasc. Dis. 2024, 3, 419-452. https://doi.org/10.3390/jvd3040033
Hayden MR. Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease. Journal of Vascular Diseases. 2024; 3(4):419-452. https://doi.org/10.3390/jvd3040033
Chicago/Turabian StyleHayden, Melvin R. 2024. "Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease" Journal of Vascular Diseases 3, no. 4: 419-452. https://doi.org/10.3390/jvd3040033
APA StyleHayden, M. R. (2024). Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease. Journal of Vascular Diseases, 3(4), 419-452. https://doi.org/10.3390/jvd3040033