Academic Journal
Synaptic changes in frontotemporal lobar degeneration: Correlation with MAPT haplotype and APOE genotype
| العنوان: | Synaptic changes in frontotemporal lobar degeneration: Correlation with MAPT haplotype and APOE genotype |
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| المؤلفون: | Connelly, S. J., Mukaetova-Ladinska, E. B., Abdul-All, Z., da Silva, J. Alves, Brayne, C., Honer, W. G., Mann, D. M A |
| المصدر: | Connelly , S J , Mukaetova-Ladinska , E B , Abdul-All , Z , da Silva , J A , Brayne , C , Honer , W G & Mann , D M A 2011 , ' Synaptic changes in frontotemporal lobar degeneration: Correlation with MAPT haplotype and APOE genotype ' , Neuropathology and Applied Neurobiology , vol. 37 , no. 4 , pp. 366-380 . https://doi.org/10.1111/j.1365-2990.2010.01150.x |
| سنة النشر: | 2011 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | APOE genotype, Frontotemporal lobar dementia, MAPT haplotype, SNAP-25, synaptophysin |
| الوصف: | Aims: 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 inSNAP-25. Conclusions: Our results suggest that synaptic expression in FTLD is influenced by a number of genetic factorswhich 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 noncognitive features of the disease. © 2011 The Authors Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://research.manchester.ac.uk/en/publications/326eb2f8-5ada-4cff-9c19-95ac828359fc |
| DOI: | 10.1111/j.1365-2990.2010.01150.x |
| الاتاحة: | https://research.manchester.ac.uk/en/publications/326eb2f8-5ada-4cff-9c19-95ac828359fc https://doi.org/10.1111/j.1365-2990.2010.01150.x |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.2873D2F3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/j.1365-2990.2010.01150.x |
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