title: Synaptic changes in frontotemporal lobar degeneration: correlation with MAPT haplotype and APOE genotype.
abstract: OBJECTIVE
  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 APOEε4 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.
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Connelly
authors.forename: E B
authors.initials: EB
authors.lastname: Mukaetova-Ladinska
authors.forename: Z
authors.initials: Z
authors.lastname: Abdul-All
authors.forename: J
authors.initials: J
authors.lastname: Alves da Silva
authors.forename: C
authors.initials: C
authors.lastname: Brayne
authors.forename: W G
authors.initials: WG
authors.lastname: Honer
authors.forename: D M A
authors.initials: DM
authors.lastname: Mann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D013569:Synapses / Q000378:metabolism*; D016708:Synaptophysin / Q000096:biosynthesis*; D050825:Synaptosomal-Associated Protein 25 / Q000096:biosynthesis*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C054369:MAPT protein, human; C494208:SNAP25 protein, human; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D016875:tau Proteins