Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: relationship with the progression of Alzheimer's disease.
The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta in the CA1 and CA3 fields of hippocampus and area 9 in 18 elderly individuals with various degrees of cognitive decline. The decrease in spinophilin-immunoreactivity was significantly related to both Braak neurofibrillary tangle (NFT) staging and clinical severity but not A beta deposition staging. The total number of spinophilin-immunoreactive puncta in CA1 field and area 9 were significantly related to MMSE scores and predicted 23.5 and 61.9% of its variability. The relationship between total number of spinophilin-immunoreactive puncta in CA1 field and MMSE scores did not persist when adjusting for Braak NFT staging. In contrast, the total number of spinophilin-immunoreactive puncta in area 9 was still significantly related to the cognitive outcome explaining an extra 9.6% of MMSE and 25.6% of the Clinical Dementia Rating scores variability. Our data suggest that neocortical dendritic spine loss is an independent parameter to consider in AD clinicopathologic correlations.
Akram
Afia
A
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Christoffel
Daniel
D
Rocher
Anne B
AB
Bouras
Constantin
C
Kövari
Enikö
E
Perl
Daniel P
DP
Morrison
John H
JH
Herrmann
François R
FR
Haroutunian
Vahram
V
Giannakopoulos
Panteleimon
P
Hof
Patrick R
PR
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D014018:Tissue Distribution; D000099273:Neurabins
D015415:Biomarkers; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000099273:Neurabins