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Microvascular pathology and vascular basement membrane components in Alzheimer's disease
1Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
Several factors have highlighted the vasculature in Alzheimer's disease (AD): Cerebral amyloid angiopathy (CAA) is common, amyloid fibrils emanate from the vascular basement membrane (VBM), and similar forms of beta-amyloid are found in vascular and parenchymal amyloid accumulations. The present article discusses the presence of microvascular pathology in AD. Microangiopathy, in addition to neurofibrillary tangles, senile plaques, and CAA, is a common pathologic hallmark of AD. VBM components are associated with amyloid plaques, and nonamyloidotic alterations of the VBM occur in brain regions susceptible to AD lesions. Also, intra-VBM perivascular cells (traditionally called pericytes), a subset of which share the immunophenotype of microglia and other mononuclear phagocytic system (MPS) cells, have been implicated in vascular alterations and cerebrovascular amyloid deposition. Perivascular and parenchymal MPS cells have access to several sources of the beta-amyloid protein precursor, including platelets, circulating white cells, and neurons. MPS cells would thus be ideally situated to uptake and process the precursor, and deposit beta-amyloid in a fashion analogous to that seen in other forms of systemic and cerebral amyloidoses.
Insights
Alzheimer's disease (AD) involves microvascular pathology, including cerebral amyloid angiopathy (CAA). Mononuclear phagocytic system (MPS) cells within blood vessels may contribute to beta-amyloid deposition in AD.
Area of Science:
- Neurology
- Pathology
- Vascular Biology
Background:
- Cerebral amyloid angiopathy (CAA) and beta-amyloid accumulation are hallmarks of Alzheimer's disease (AD).
- Microvascular pathology, including alterations in the vascular basement membrane (VBM), is prevalent in AD.
- Perivascular cells, identified as mononuclear phagocytic system (MPS) cells, are implicated in vascular changes and amyloid deposition.
Purpose of the Study:
- To discuss the presence and role of microvascular pathology in Alzheimer's disease.
- To explore the involvement of VBM components and perivascular MPS cells in AD pathogenesis.
- To investigate the potential mechanisms of beta-amyloid deposition by MPS cells in the cerebrovasculature.
Main Methods:
- Review of existing literature on AD neuropathology, focusing on vascular aspects.
- Analysis of the association between VBM components and amyloid plaques.
- Immunophenotypic characterization of intra-VBM perivascular cells and their relation to MPS.
Main Results:
- Microangiopathy is a common pathological feature of AD, alongside neurofibrillary tangles and senile plaques.
- VBM alterations occur in AD-vulnerable brain regions and are linked to amyloid plaques.
- Intra-VBM perivascular cells, sharing MPS cell characteristics, are involved in vascular alterations and amyloid deposition.
Conclusions:
- Microvascular pathology, particularly microangiopathy and CAA, is integral to Alzheimer's disease.
- Vascular basement membrane alterations and perivascular MPS cells play significant roles in AD cerebrovascular amyloidosis.
- MPS cells are strategically positioned to contribute to beta-amyloid precursor processing and deposition in the brain vasculature.