help button home button Am J Pathol International Conference on Pathology of Chest Diseases
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Order Full text via Infotrieve
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by de la Monte, S. M.
Right arrow Articles by Hsu, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de la Monte, S. M.
Right arrow Articles by Hsu, D. W.

American Journal of Pathology, Vol 147, 934-946, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Aberrant GAP-43 gene expression in Alzheimer's disease

SM de la Monte, SC Ng and DW Hsu
Alzheimer's Disease Research Center, Neuropathology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

GAP-43 is a growth-associated phosphoprotein expressed at high levels in neurons during development, axonal regeneration, and neuritic sprouting. GAP-43 gene expression in mature neurons is probably functionally important for the structural remodeling of synapses as required for learning and establishing new memory. The widespread aberrant neuritic growth accompanied by impaired synaptic plasticity in Alzheimer's disease (AD) suggests that abnormal GAP-43 gene expression may contribute to the cascade of neurodegeneration. In the present study, end-stage AD brains exhibited reduced neuronal expression but increased glial cell levels of GAP-43 mRNA and protein. Glial cell localization of GAP-43 gene expression was confirmed by in situ hybridization of cerebral tissue, Northern blot analysis of microdissected cerebral white matter, and independent analysis of astrocytoma cell lines and primary malignant astrocytomas. In addition, in AD, GAP-43 immunoreactivity was translocated from the cytosol to membranes of swollen neuritic (dendritic) and glial cell processes throughout cerebral cortex and white matter. Downregulated and aberrant neuronal GAP-43 gene expression appears to reflect an important molecular lesion that precedes and progresses with the widespread synaptic disconnection and dementia in AD. At the same time, the presence of similar neuronal abnormalities in Pick's disease, diffuse Lewy body disease, Parkinson's disease, and Down syndrome suggests common mechanisms in the respective cascades of neurodegeneration. Finally, the finding of aberrantly increased glial cell GAP-43 gene expression in AD exposes a previously unrecognized neurodegenerative change that may account for the axonal loss and white matter atrophy detected early in the course of disease.


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
M. C. Irizarry, F. Soriano, M. McNamara, K. J. Page, D. Schenk, D. Games, and B. T. Hyman
Abeta Deposition Is Associated with Neuropil Changes, but not with Overt Neuronal Loss in the Human Amyloid Precursor Protein V717F (PDAPP) Transgenic Mouse
J. Neurosci., September 15, 1997; 17(18): 7053 - 7059.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Maemura, S. M. de la Monte, M. T. Chin, M. D. Layne, C.-M. Hsieh, S.-F. Yet, M. A. Perrella, and M.-E. Lee
CLIF, a Novel Cycle-like Factor, Regulates the Circadian Oscillation of Plasminogen Activator Inhibitor-1 Gene Expression
J. Biol. Chem., November 17, 2000; 275(47): 36847 - 36851.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1995 by the American Society for Investigative Pathology.