Morphology of Alzheimer’s disease and related disorders

Summary

The diagnosis of Alzheimer’s disease (AD) can made with certainty only by histological examination of the brain, either on biopsy or at autopsy, using current criteria that are critically discussed. The morphologic diagnosis of AD is based on the finding of more than certain minimum age-related numbers of neuritic plaques (NP) and neurofibrillary tangles (NFT) that may occur independently from each other and show specific, often bilaterally symmetrical distribution patterns. Although both NFT and NP represent useful diagnostic markers and their concentrations in neocortex correlate reasonably well with certain mental status tests and some biochemical data, progressive loss of neurons and synapses in cortex and brainstem appear to be more correlated with both dementia and neuromediator changes, but their causal relationship with amyloid deposition and cytoskeletal lesions is not clear. Cortical atrophy with 40 to 60% loss of large neurons and 45 to 55% decline of synaptic density in frontal, temporal, parietal cortex and hippocampus are probable correlates of progressive dementia. Many mediator specific brainstem nuclei show progressive neuronal loss and presence of NFT with severe involvement of cholinergic nucleus basalis of Meynert (15 to 90% cell loss and atrophy of large neurons), pedunculopontine and Westphal-Edinger nuclei, serotonergic dorsal raphe nucleus (10 to 76% cell loss), noradrenergic locus ceruleus (40 to 80% cell loss in topographic relation to temporal targets) and, less, the dopaminergic striatonigral system. The morphologic heterogeneity of AD shows overlaps with Parkinson’s, diffuse Lewy body disease, cerebrovascular and other brain lesions. In autopsy series, the accuracy rates for clinical diagnosis of AD are about 80 to 85%, but more standardized morphologic criteria are needed.