TY - JOUR
T1 - Loss of basal forebrain p75NTR immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease
AU - Mufson, Elliott J.
AU - Ma, Shuang Y.
AU - Dills, John
AU - Cochran, Elizabeth J.
AU - Leurgans, Sue
AU - Wuu, Joanne
AU - Bennett, David A.
AU - Jaffar, Syed
AU - Gilmor, Michelle L.
AU - Levey, Alan I.
AU - Kordower, Jeffrey H.
PY - 2002/2/4
Y1 - 2002/2/4
N2 - The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75NTR), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75NTR-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75NTR-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75NTR CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.
AB - The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75NTR), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75NTR-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75NTR-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75NTR CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.
KW - Alzheimer's disease
KW - Cholinergic
KW - Dementia
KW - Neurotrophin receptor
KW - Nucleus basalis
KW - Stereology
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U2 - 10.1002/cne.10122
DO - 10.1002/cne.10122
M3 - Article
C2 - 11793352
AN - SCOPUS:0037016848
SN - 0021-9967
VL - 443
SP - 136
EP - 153
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 2
ER -