Brain Parenchymal and Microvascular Amyloid in Alzheimer's Disease

Abstract

Brains of patients with Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily in the form of characteristic parenchymal 'plaques' (senile or neuritic plaques/SP's) and as mural deposits in the walls of capillaries and arterioles (cerebral amyloid angiopathy /CAA). A major component of this amyloid is a small and unique peptide composed of 39-43 amino acids, beta/A4, which is cleaved from a much larger precursor protein (APP) that has several isoforms. Brain amyloid can be detected in autopsy or biopsy brain tissue by classical, immunohistochemical and ultrastructural (including immuno-electron microscopic) methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is remarkably variable (e.g. predominantly parenchymal or vascular, or a mixture of parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis of the neurological deficit, neocortical atrophy and progressive synapse loss associated with AD/SDAT has yet to be determined. However, mutations in the gene that encodes APP are clearly associated with familial AD syndromes in which there is significant brain amyloid deposition. CAA, in addition to its association with AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work with recently developed transgenic mice which express large amounts of beta/A4 in the central nervous system is likely to elucidate mechanisms by which the protein is selectively or deposited in the brain in a parenchymal or microvascular form, and how it contributes to the pathogenesis of neurodegeneration.

Histological and immunohistochemical characteristics of cerebral amyloid angiopathy in elderly dogs

“…In the moderate form, the tunica media is thicker than normal and is replaced by deposits of Ab amyloid, with no evidence of blood leakage. The massive deposits of Ab with focal wall fragmentation and at least one focus of perivascular leakage as evidenced by the presence of erythrocytes or hemosiderin, or both, are characteristics of the severe form (Vonsattel et al 1991;Vinters et al 1996;Revesz et al 2002;Kumar-Singh 2008;Mendel et al 2013). In this study, CAA has been classified according to the Vonsattel scale.…”

“…Other structural changes such as microangiopathy, microaneurysmal dilatation, necrosis, etc. can also be observed in the cerebral blood vessel walls (Vinters et al 1996;Revesz et al 2002;Kumar-Singh 2008). Furthermore, CAA independently contributes to dementia and it is a risk factor for hemorrhagic stroke (KumarSingh 2008).…”

“…This abnormal protein accumulates in the wall of all blood vessel types of the cerebrum and cerebellum gray matter. Deposits of amyloid are rarely present in the blood vessels of white matter (Vinters et al 1996;Revesz et al 2002;Kumar-Singh 2008). It has been widely accepted that Ab in the wall of cerebral vasculature is toxic to the vascular elements and causes structural and functional alterations of the blood vessels.…”

“…The sporadic form occurs much more frequently and mostly as a sporadic condition in the elderly, with an increasing incidence associated with age. This form is a very common finding in the brain of patients with Alzheimer's disease (AD) (Vinters et al 1996;Revesz et al 2002;Kumar-Singh 2008;Mendel et al 2013). CAA in the animal brain is also related to aging (Walker 1997;Borras et al 1999).…”

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

“…In amyloid angiopathy, beta-amyloid deposits in the walls of arteries and arterioles result in a narrowed lumina and eventually occlusion (Ellis et al 1996;Vinters et al 1996;Jellinger 2002;Tian et al 2006). The retinal vascular changes in AD include narrow veins, decreased retinal blood flow in veins, reduced complexity of the branching pattern, reduced optimality of the branching geometry and less tortuous venules (Heaton et al 2015).…”