Neuronal activity and early neurofibrillary tangles in Alzheimer's disease

Kimmo Hatanpää, Daniel R. Brady, James Stoll, Stanley I. Rapoport, Krish Chandrasekaran

Research output: Contribution to journalArticle

63 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)411-420
Number of pages10
JournalAnnals of Neurology
Volume40
Issue number3
StatePublished - Sep 1996

Fingerprint

Neurofibrillary Tangles
Alzheimer Disease
Neurons
Electron Transport Complex IV
Messenger RNA
Brain
Mitochondrial DNA
Synaptic Transmission
Energy Metabolism
In Situ Hybridization
Down-Regulation
Pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hatanpää, K., Brady, D. R., Stoll, J., Rapoport, S. I., & Chandrasekaran, K. (1996). Neuronal activity and early neurofibrillary tangles in Alzheimer's disease. Annals of Neurology, 40(3), 411-420.

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease. / Hatanpää, Kimmo; Brady, Daniel R.; Stoll, James; Rapoport, Stanley I.; Chandrasekaran, Krish.

In: Annals of Neurology, Vol. 40, No. 3, 09.1996, p. 411-420.

Research output: Contribution to journalArticle

Hatanpää, K, Brady, DR, Stoll, J, Rapoport, SI & Chandrasekaran, K 1996, 'Neuronal activity and early neurofibrillary tangles in Alzheimer's disease', Annals of Neurology, vol. 40, no. 3, pp. 411-420.
Hatanpää K, Brady DR, Stoll J, Rapoport SI, Chandrasekaran K. Neuronal activity and early neurofibrillary tangles in Alzheimer's disease. Annals of Neurology. 1996 Sep;40(3):411-420.
Hatanpää, Kimmo ; Brady, Daniel R. ; Stoll, James ; Rapoport, Stanley I. ; Chandrasekaran, Krish. / Neuronal activity and early neurofibrillary tangles in Alzheimer's disease. In: Annals of Neurology. 1996 ; Vol. 40, No. 3. pp. 411-420.
@article{05d3f66fbd114154b213581c14fb6895,
title = "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.",
author = "Kimmo Hatanp{\"a}{\"a} and Brady, {Daniel R.} and James Stoll and Rapoport, {Stanley I.} and Krish Chandrasekaran",
year = "1996",
month = "9",
language = "English (US)",
volume = "40",
pages = "411--420",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Neuronal activity and early neurofibrillary tangles in Alzheimer's disease

AU - Hatanpää, Kimmo

AU - Brady, Daniel R.

AU - Stoll, James

AU - Rapoport, Stanley I.

AU - Chandrasekaran, Krish

PY - 1996/9

Y1 - 1996/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029811758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029811758&partnerID=8YFLogxK

M3 - Article

VL - 40

SP - 411

EP - 420

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -