Neuropathological aspects of Alzheimer disease

In the present review we describe the morphological features of Alzheimer's disease (AD) and compare these findings with those obtained in argyrophilic grain disease, a frequent but often unrecognized form of late-onset dementia. Macroscopically AD brains exhibit a marked atrophy of the medical temporal lobe, including the hippocampus, entorhinal cortex and amygdala. Neuronal loss, decreased synapse density and the intra- and extracellular deposition of abnormal proteins constitute the histological hallmark lesions of AD. The intraneural accumulation of the microtubule-associated protein tau in a hyperphosphorylated state leads to the formation of neurofibrillary lesions (NFL). Whereas the widespread distribution of NFL in the neocortex correlates with the cognitive decline in AD patients no such correlation could be found for the extracellular deposition of the A beta-protein in the shape of senile plaques (SP). However, dementia correlates with the amount of neuritic degeneration within a subtype of SP ('neuritic plaques'). We further discuss some of the risk factors for AD, i.e. the genetic risk factors.