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Shift in the ratio of three‐repeat tau and four‐repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease
Author(s) -
Ginsberg Stephen D.,
Che Shaoli,
Counts Scott E.,
Mufson Elliott J.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03641.x
Subject(s) - basal forebrain , nucleus basalis , tauopathy , neuroscience , cholinergic neuron , cholinergic , tau protein , biology , neurofibrillary tangle , hippocampal formation , alzheimer's disease , tangle , neurodegeneration , psychology , disease , senile plaques , medicine , mathematics , pure mathematics
Molecular mechanisms underlying tauopathy remain undetermined. In the current study, single cell gene expression profiling was coupled with custom‐designed cDNA array analysis to evaluate tau expression and other cytoskeletal elements within individual neuronal populations in patients with no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Results revealed a shift in the ratio of three‐repeat tau (3Rtau) to four‐repeat tau (4Rtau) mRNAs within individual human cholinergic basal forebrain (CBF) neurons within nucleus basalis (NB) and CA1 hippocampal neurons during the progression of AD, but not during normal aging. A shift in 3Rtau to 4Rtau may precipitate a cascade of events in the selective vulnerability of neurons, ultimately leading to frank neurofibrillary tangle (NFT) formation in tauopathies including AD.