Premium
Is the neuronal basis of Alzheimer's disease cholinergic or glutamatergic?
Author(s) -
Palmer Alan M.,
Gershon Samuel
Publication year - 1990
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.4.10.2165009
Subject(s) - nucleus basalis , basal forebrain , choline acetyltransferase , cholinergic , cholinergic neuron , glutamatergic , neuroscience , dementia , alzheimer's disease , hippocampus , acetylcholine , glutamate receptor , cerebral cortex , disease , biology , psychology , medicine , endocrinology , receptor
The hypothesis that the symptomatology of Alzheimer's disease is attributable to cholinergic dysfunction is supported by postmortem studies that have demonstrated reduced choline acetyltransferase (ChAT) activity across all areas of cerebral cortex and diminished numbers of perikarya in the basal forebrain nucleus basalis of Meynert. Biopsy studies of ChAT activity, choline uptake, and acetylcholine synthesis also suggest that cholinergic denervation occurs relatively early in the course of the disease, and in confirmation of postmortem data, correlates with the severity of cognitive impairment. An alternative hypothesis to explain the dementia of Alzheimer's disease is the glutamatergic hypothesis. This is based largely on postmortem evidence indicating reduced binding and uptake of D[ 3 H]aspartate, as well as loss of a number of other putative markers, such as phosphate‐activated glutaminase activity, glutamate concentration, and the number of pyramidal cell perikarya, with this latter change correlating with the severity of dementia. Shortcomings of each hypothesis are discussed and the merits of single neuron hypotheses to explain the dementia of Alzheimer's disease are considered.— P almer , A. M.; G ershon , S. I s the neuronal basis of Alzheimer's disease cholinergic or glutamatergic? FASEB J. 4: 2745‐2752; 1990.