There was a correlation between neuropathology and apoptosis (programmed cell death) in the hippocampus of Alzheimer's disease (AD) brains, but no evidence of apoptosis in cells with neurofibrillary tangles. The perirhinal, middle and inferior temporal cortices exhibited more dystrophic neurites than the superior temporal cortex, with laminae 2-3 most severely affected. We developed several approaches to elucidating the molecular basis of selective regional vulnerability in AD. Monoclonal antibodies were generated against the entorhinal cortex or basolateral amygdala using the SOFISTIC technique, which labeled subcellular compartments of neurons as well as neurofibrillary tangles. Brain specific expression of human microtubule-associated protein 1A (MAP1A) gene was demonstrated and assigned to human chromosome 15. In situ hybridization revealed a deficit in cytochrome oxidase (COX) activity and of messenger RNA (mRNA) expression in association brain regions in AD, in neurons which were stained by an antibody for paired helical filaments (PHF), a constituent of NFTs. Thus, neurons expressing PHFs retain some capacity for oxidative phosphorylation. A brain bank was established to provide appropriate tissue for neuropathological studies in AD. AD patients with clinically leukoencephalopathy revealed on postmortem severe cortical amyloid angiopathy without involvement of white matter vessels or atherosclerosis.
