Gap-43 message levels in anterior cerebellum in Alzheimer's disease

Janet E. Cheetham, Mark R. Martzen, Ann Marie Kazee, Paul D. Coleman

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

We have previously reported that decreased growth-associated protein (GAP-43) message in frontal association cortex (area 9) of Alzheimer's disease (AD) patients is associated with increased density of neurons containing neurofibrillary tangles (NFTs). This finding leads to the hypothesis that decreased GAP-43 message in AD may be related to NFTs, rather than to some other aspect of AD pathology. Therefore, we predicted that in areas of brain unaffected by NFTs in AD the GAP-43 message levels should be similar to those of controls. The cerebellum is known to have a number of pathologies of AD, including diffuse plaques (DPs), microglial activation and reactive astrocytes. NFTs, however, are not typically found in the cerebellum mRNA was extracted from anterior cerebellum of AD and control cases, Northern- and slot-blotted and hybridized against a GAP-43 probe. Poly(dT) and glucose-3-phosphate dehydrogenase probes were used for normalization. The average relative GAP-43 message level was 0.582 in the AD cases and 0.448 in control cases. This 23% difference failed to reach statistical significance. Regression analysis within the AD group demonstrated that GAP-43 message level in cerebellar cortex was not significantly correlated with diffuse plaque density in cerebellar cortex. GAP-43 message levels in cerebellar cortex were also not correlated with summed density of neuritic plaques or summed density of NFTs in cortical regions - here used as an index of severity of disease. The data reported here also emphasize that the (NFT-dependent) reduction in GAP-43 mRNA levels previously reported in frontal association cortex in Alzheimer's disease appears to be region specific and not a general brain phenomenon. The preservation of normal GAP-43 message levels in the cerebellum in AD is consistent with the hypothesis that events related to NFT formation have a major impact on the expression of GAP-43 in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalMolecular Brain Research
Volume36
Issue number1
DOIs
StatePublished - Feb 1996

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Keywords

  • Alzheimer's disease
  • Cerebellum
  • Diffuse plaque
  • GAP-43
  • Neuritic plaque
  • Neurofibrillary tangle
  • mRNA levels

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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