Abstract
We examined the associations of postmortem neocortical immunoreactivities for microglia, astrocytes, Aβ and Tau with cognitive changes in clinically characterized subjects with pathological diagnoses (CERAD classification) of definite AD (9), possible AD (15) and age-matched controls (11). By measuring the fractional area (FA) of immunoreactivity, we found that Aβ deposits appear early in the pathogenesis of Aβ, but cannot account for cognitive decline. We found a significant increases in FA for microglia in possible AD cases (nondemented) compared to controls ( P<0.05) and in FA for astrocytes in definite AD (demented) compared to possible AD ( P<0.01). Tau immunoreactivity was observed only in the neuropil of definite AD cases ( P<0.001). The significant increase in microglia between controls and AD possible cases suggests that activation of microglia occurs in the early pathogenesis of AD, whereas the significant association between astrocytic reaction and dementia, suggests that these cells play a role in the late stage of the disease, when dementia develops. Tau immunoreactivity appears as the strongest morphological correlate of dementia.
Highlights
In Alzheimer’s disease (AD), amyloid -peptide (Apeptide) is deposited in the brain parenchyma and cerebral blood vessels
We observed a significant increase in the fractional area of reactive microglia associated with the transition from controls to possible AD cases, suggesting that microglia are important in the early pathogenesis of AD
Some Senile plaques (SP) were IR only for A but not for astrocytes or microglia. The majority of these SP were of the diffuse type and most were found among possible AD cases
Summary
In Alzheimer’s disease (AD), amyloid -peptide (Apeptide) is deposited in the brain parenchyma and cerebral blood vessels. In the CNS, astrocytes are important for maintaining homeostasis [6,18,21,28,37,48,49] and have an important role in immune responses. These cells can migrate in response to chemotactic stimuli and gather in areas of injury or inflammation. They can produce complement, complement receptors, and cytokines (especially pro-inflammatory) [10,39]
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