Neuronal activity and early neurofibrillary tangles in Alzheimer's disease.

Abstract:

:We studied neuronal activity and its relation to the accumulation of neurofibrillary tangles in Alzheimer's disease (AD) neurons by in situ hybridization to cytochrome oxidase subunit III messenger RNA, a marker of mitochondrial energy metabolism. In AD midtemporal cortex, levels of cytochrome oxidase subunit III messenger RNA were decreased by 26% in neurons bearing early-stage neurofibrillary tangles as compared to tangle-free neurons (p < 0.01). However, levels of 12S ribosomal RNA, also encoded by mitochondrial DNA, and of total messenger RNA were decreased only in later stages of tangle development. Comparing tangle-free neurons of 4 AD brains to tangle-free neurons of 3 control brains, levels of cytochrome oxidase subunit III messenger RNA were found to be 25% lower (p < 0.001) in AD tangle-free neurons. Because energy metabolic needs of neurons are mainly determined by synaptic input, the observed decreases in cytochrome oxidase subunit III messenger RNA likely reflect downregulation due to impaired synaptic function in AD. Thus, a failure in synaptic transmission may precede tangle formation. A further decline in neuronal activity is seen as tangle formation progresses. However, these results can also be viewed as showing the viability and continuing activity, albeit at a lower level, of neurons in the early stages of neurofibrillary pathology.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Hatanpää K,Brady DR,Stoll J,Rapoport SI,Chandrasekaran K

doi

10.1002/ana.410400310

subject

Has Abstract

pub_date

1996-09-01 00:00:00

pages

411-20

issue

3

eissn

0364-5134

issn

1531-8249

journal_volume

40

pub_type

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