As in the case of cell and synaptic loss, cell pathology also occurs in the normal aging brain, but the number of affected structures is quite small and confined to discrete areas (e.g., the hippocampus). This contrasts with the extensive pathology associated with most neurodegenerative diseases (e.g., AD, PD, multi-infarct dementia) (49).
Major cell pathologic changes are of a degenerative nature (i.e., progressively leading to impaired function and death) and are manifested by the following:
■ Intracellular accumulation of abnormal inclusions such as lipofuscin, melanin, Lewy bodies, and neurofibrillary and amyloid proteins
■ Extracellular accumulation of abnormal amyloid proteins in NPs and surrounding cerebral blood vessels [perhaps deriving from the systemic circulation through defects of the blood-brain barrier (BBB) permeability], and of ubiquitin, hyperphosphorylated tau proteins, and other abnormal proteins
■ Vascular (atherosclerotic) alterations that may induce hemorrhages and infarcts (strokes) consequent to rupture or obstruction of blood vessels (as in multi-infarct dementia)
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