Premium
Synaptic changes in frontotemporal lobar degeneration: correlation with MAPT haplotype and APOE genotype
Author(s) -
Connelly S. J.,
MukaetovaLadinska E. B.,
AbdulAll Z.,
Alves da Silva J.,
Brayne C.,
Honer W. G.,
Mann D. M. A.
Publication year - 2011
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2010.01150.x
Subject(s) - frontotemporal lobar degeneration , synaptophysin , haplotype , apolipoprotein e , neuropathology , alzheimer's disease , pathology , tau protein , genotype , psychology , neuroscience , biology , frontotemporal dementia , medicine , dementia , immunohistochemistry , disease , genetics , gene
S. J. Connelly, E. B. Mukaetova‐Ladinska, Z. Abdul‐All, J. Alves da Silva, C. Brayne, W. G. Honer and D. M. A. Mann (2011) Neuropathology and Applied Neurobiology 37, 366–380
Synaptic changes in frontotemporal lobar degeneration: correlation with MAPT haplotype and APOE genotypeAims: This immunohistochemical study quantified synaptic changes (synaptophysin and SNAP‐25) in the frontal lobe of subjects with frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), and related these to APOE genotype and MAPT haplotype. Methods: Frontal neocortex (BA9) of post mortem brains from subjects with FTLD ( n = 20), AD ( n = 10) and age‐matched controls ( n = 9) were studied immunohistochemically for synaptophysin and SNAP‐25. Results: We report that patients with FTLD have a significant increase in synaptophysin and depletion in SNAP‐25 proteins compared to both control subjects and individuals with AD ( P < 0.001). The FTLD up‐regulation of synaptophysin is disease specific ( P < 0.0001), and is not influenced by age ( P = 0.787) or cortical atrophy ( P = 0.248). The SNAP‐25 depletion is influenced by a number of factors, including family history and histological characteristics of FTLD, APOE genotype, MAPT haplotype and gender. Thus, more profound loss of SNAP‐25 occurred in tau‐negative FTLD, and was associated with female gender and lack of family history of FTLD. Presence of APOE ε4 allele and MAPT H2 haplotype in FTLD had a significant influence on the expression of synaptic proteins, specifically invoking a decrease in SNAP‐25. Conclusions: Our results suggest that synaptic expression in FTLD is influenced by a number of genetic factors which need to be taken into account in future neuropathological and biochemical studies dealing with altered neuronal mechanisms of the disease. The selective loss of SNAP‐25 in FTLD may be closely related to the core clinical non‐cognitive features of the disease.