Reduced GAP-43 message levels are associated with increased neurofibrillary tangle density in the frontal association cortex (area 9) in Alzheimer's disease

Paul Coleman, Ann Marie Kazee, Lowell Lapham, Thomas Eskin, Kathryn Rogers

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We previously suggested the hypothesis that defective neuronal plasticity is a major neurobiological deficit causing the dementia of Alzheimer's disease (AD). We used message levels of the growth-associated protein, GAP-43, as a marker of axonal plasticity to examine the hypothesis of defective neuronal plasticity in AD. When all AD cases are combined, the average level of GAP-43 message in area 9 of the AD frontal association cortex was not significantly different from the level in the comparably aged control cortex. Differentiation of AD cases on the basis of neurofibrillary tangle (NFT) density revealed that in AD cases with high tangle density average GAP-43 message level was reduced fivefold relative to levels in AD cases with low NFT density. AD cases with low neurofibrillary tangle density had levels of GAP-43 message that were not significantly different from the levels of normal controls. Differentiation of AD cases on the basis of neuritic plaque density did not indicate as strong a relationship to GAP-43 message level. The association between neurofibrillary tangle density and GAP-43 message level suggests the hypothesis that neurofibrillary tangles may reduce GAP-43 expression. Data of others show a relationship between high NFT density and reduced levels of synaptophysin-like immunoreactivity and reduced cerebral glucose metabolism. These data combine to suggest a set of AD cases with high NFT density, reduced axonal plasticity, reduced synaptic density, and reduced cerebral glucose metabolism-all variables that may be directly related to the functioning of the brain. On the other hand, there also exist AD cases with low NFT density and normal levels of GAP-43 message, synaptophysin-like immunoreactivity, and cerebral glucose metabolism. Yet, these cases are also demented. These results emphasize the heterogeneity of AD cases and the necessity for extensive knowledge of the clinical and pathologic characteristics of the cases in a study sample.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalNeurobiology of Aging
Volume13
Issue number6
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

GAP-43 Protein
Neurofibrillary Tangles
Frontal Lobe
Alzheimer Disease
Neuronal Plasticity
Synaptophysin
Glucose
Alzheimer Disease 9
Amyloid Plaques
Dementia

Keywords

  • Aging
  • Alzheimer's disease
  • Association cortex
  • GAP-43
  • Message levels
  • Neurofibrillary tangles

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Reduced GAP-43 message levels are associated with increased neurofibrillary tangle density in the frontal association cortex (area 9) in Alzheimer's disease. / Coleman, Paul; Kazee, Ann Marie; Lapham, Lowell; Eskin, Thomas; Rogers, Kathryn.

In: Neurobiology of Aging, Vol. 13, No. 6, 01.01.1992, p. 631-639.

Research output: Contribution to journalArticle

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abstract = "We previously suggested the hypothesis that defective neuronal plasticity is a major neurobiological deficit causing the dementia of Alzheimer's disease (AD). We used message levels of the growth-associated protein, GAP-43, as a marker of axonal plasticity to examine the hypothesis of defective neuronal plasticity in AD. When all AD cases are combined, the average level of GAP-43 message in area 9 of the AD frontal association cortex was not significantly different from the level in the comparably aged control cortex. Differentiation of AD cases on the basis of neurofibrillary tangle (NFT) density revealed that in AD cases with high tangle density average GAP-43 message level was reduced fivefold relative to levels in AD cases with low NFT density. AD cases with low neurofibrillary tangle density had levels of GAP-43 message that were not significantly different from the levels of normal controls. Differentiation of AD cases on the basis of neuritic plaque density did not indicate as strong a relationship to GAP-43 message level. The association between neurofibrillary tangle density and GAP-43 message level suggests the hypothesis that neurofibrillary tangles may reduce GAP-43 expression. Data of others show a relationship between high NFT density and reduced levels of synaptophysin-like immunoreactivity and reduced cerebral glucose metabolism. These data combine to suggest a set of AD cases with high NFT density, reduced axonal plasticity, reduced synaptic density, and reduced cerebral glucose metabolism-all variables that may be directly related to the functioning of the brain. On the other hand, there also exist AD cases with low NFT density and normal levels of GAP-43 message, synaptophysin-like immunoreactivity, and cerebral glucose metabolism. Yet, these cases are also demented. These results emphasize the heterogeneity of AD cases and the necessity for extensive knowledge of the clinical and pathologic characteristics of the cases in a study sample.",
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