The neuropathology of aminergic nuclei in Alzheimer's disease

Neuronal loss and the presence of neurofibrillary tangles (NFTs) within aminergic nuclei were examined in a series of patients with Alzheimer's disease (AD). Neuromelanin-containing neurons within the locus ceruleus and large nucleolus-containing neurons within the dorsal raphe nucleus and the central superior (raphe) nucleus were counted in 25 patients with AD and in 12 age-matched control subjects. Numbers of NFTs were quantified in the same regions. Counts were compared with clinical data, including psychiatric evaluations, available for 21 of the patients with AD. Within the locus ceruleus in the patients with AD, abnormalities were more severe at mid level than at caudal or rostral levels (p less than 0.01). Within the dorsal raphe nucleus, neuronal loss was most severe caudally (p less than 0.05). NFTs, but not neuronal loss, were demonstrated within the central superior nucleus. Neuronal and NFT counts did not correlate at individual levels; the relative severity of both pathological processes was consistent from level to level within nuclei but was less consistent between nuclei. Neuronal loss correlated inversely with age, particularly within the locus ceruleus. Duration of disease correlated inversely with counts of NFTs, particularly within the dorsal raphe nucleus, implying a correlation between NFT counts and rate of progression of disease as all but 3 patients had severe dementia. Significantly, patients with AD complicated by major depression had fewer neurons at the mid level of the locus ceruleus and at the rostral level of the central superior nucleus in comparison with nondepressed patients. There was a trend suggesting greater loss of neurons at all levels of the locus ceruleus and dorsal raphe nucleus in depressed individuals.