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PMID: 9176387 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease.

The American journal of pathology ·Vol. 150 ·No. 6 ·1997-06-00 ·Pages 1933-9

McShea A, Harris PL, Webster KR, Wahl AF, Smith MA

Abstract

In this study, we demonstrate that two important regulators of the cell cycle, cyclin-dependent kinase-4 and its inhibitor p16, are increased in the brains of cases of Alzheimer's disease patients compared with age-matched controls. Both proteins are increased in the pyramidal neurons of the hippocampus, including those neurons containing neurofibrillary tangles and granulovacuolar degeneration. As p16 is not normally found in terminally differentiated neurons, it seems paradoxical that it is increased in Alzheimer's disease unless it is responding to increases in cyclin-dependent kinase-4 or other cell cycle regulators. Induction of the latter, a protein that signals re-entry and progression through the cell cycle, may itself be the consequence of alpha response to a growth stimulus. Re-entry into the cell cycle is likely deleterious in terminally differentiated neurons and may contribute to the biochemical abnormalities, such as oxidative stress and hyperphosphorylated tau protein, as well as the neuronal degeneration characteristic of the pathology of Alzheimer's disease.

MeSH Terms
Alzheimer Disease/metabolism Brain/metabolism Carrier Proteins/metabolism Cell Cycle Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinases/metabolism Enzyme Inhibitors/metabolism Humans Immunohistochemistry Neurofibrillary Tangles/metabolism Proto-Oncogene Proteins Recombinant Fusion Proteins/metabolism
Chemicals
Carrier Proteins Cyclin-Dependent Kinase Inhibitor p16 Enzyme Inhibitors Proto-Oncogene Proteins Recombinant Fusion Proteins CDK4 protein, human Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
McShea A
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington, USA.
Harris P L
Webster K R
Wahl A F
Smith M A
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1997-06-00
Pages
1933-9
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1858317
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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