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Fibroblast glutamate transport in aging and in AD: correlations with disease severity.

Abstract：

:Altered glutamate transport and aberrant EAAT1 expression were shown in Alzheimer's disease (AD) brains. It is presently unknown whether these modifications are a consequence of neurodegeneration or play a pathogenetic role. However, recent findings of decreased glutamate uptake, EAAT1 protein and mRNA in AD platelets suggest that glutamate transporter modifications may be systemic and might explain the decreased glutamate uptake. We now used primary fibroblast cultures from 10 AD patients to further investigate the specific involvement of glutamate transporters in this disorder and in normal aging. Decreased glutamate uptake (p<0.001), EAAT1 expression (p<0.05) and mRNA (p<0.01) were observed in aged people, compared to younger controls. In AD fibroblasts, compared to age-matched controls, we observed further reductions of glutamate uptake (p<0.0005) and EAAT1 expression (p<0.005), while EAAT1 mRNA increase (p<0.001) was shown. EAAT1 parameters were mutually correlated (p<0.01) and correlations were shown with dementia severity (p<0.05 MMSE-expression, p<0.005 MMSE-mRNA). We suggest fibroblast cultures as possible ex vivo peripheral model to study the glutamate involvement and possible molecular and therapeutic targets in AD.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Zoia CP,Tagliabue E,Isella V,Begni B,Fumagalli L,Brighina L,Appollonio I,Racchi M,Ferrarese C

doi

10.1016/j.neurobiolaging.2004.07.007

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

825-32

issue

6

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(04)00258-1

journal_volume

26

pub_type

临床试验,杂志文章

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