Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(sw) mice

Mounting evidence suggests that cholesterol may contribute to the pathogene sis of Alzheimer disease (AD). We examined whether cholesterol might be pre sent in senile plaques. a hallmark neuropathological feature of AD. We empl oyed 2 different fluorometric-staining techniques (filipin staining and an enzymatic technique) for the determination of cholesterol in brains of post mortem confirmed AD patients and in nondemented, age-matched histopathologi cally normal controls. AD patient brains showed abnormal accumulation of ch olesterol in congophilic/birefringent dense cores of senile plaques that wa s essentially absent in histopathologically normal controls. To determine w hether increased senile plaque-associated cholesterol occurred generally in all plaques or was restricted to a specific subset, quantitative analysis was performed. Data indicate abnormal accumulation of cholesterol in cores of mature plaques but not in diffuse or immature plaques. Additionally, tra nsgenic mice that overexpress the "Swedish" amyloid precursor protein (Tg A PP(vw) line 2576) exhibited a similar pattern of abnormal cholesterol accum ulation in mature, congophilic amyloid plaques at 24 months of age that was absent in their control littermate., or in 8-month-old Tg APP(vw) mice (an age prior to amyloid deposition). Taken together, our results imply a link between cholesterol and AD pathogenesis and suggest that cholesterol plays an important role in the formation and/or progression of senile plaque.