Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype.
We have investigated the extent and pattern of immunostaining for ubiquitin protein (UBQ) in 60 patients with frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U), 37 of whom were ascertained in Manchester UK and 23 in Newcastle-Upon-Tyne, UK. There were three distinct histological patterns according to the form and distribution of the UBQ pathology. Histological type 1 was present in 19 patients (32%) and characterised by the presence of a moderate number, or numerous, UBQ immunoreactive neurites and intraneuronal cytoplasmic inclusions within layer II of the frontal and temporal cerebral cortex, and cytoplasmic inclusions within granule cells of the dentate gyrus; neuronal intranuclear inclusions (NII) of a "cat's eye" or "lentiform" appearance were present in 17 of these patients. In histological type 2 (16 patients, 27%), UBQ neurites were predominantly, or exclusively, present with few intraneuronal cytoplasmic inclusions within layer II of the cerebral cortex, while in histological type 3 (25 patients, 42%), UBQ intraneuronal cytoplasmic inclusions either within the cortical layer II or in the granule cells of the dentate gyrus, with few or no UBQ neurites, were seen. In neither of these latter two groups were NII present. The influence of histological type on clinical phenotype was highly significant with type 1 histology being associated clinically with cases of frontotemporal dementia (FTD) or progressive non-fluent aphasia (PNFA), type 2 histology with semantic dementia (SD), and type 3 histology with FTD, or FTD and motor neurone disease (MND).
Mackenzie
Ian R A
IR
Department of Pathology, Vancouver General Hospital, V5Z 1M9, Vancouver, BC, Canada.
Baborie
Atik
A
Pickering-Brown
Stuart
S
Du Plessis
Daniel
D
Jaros
Evelyn
E
Perry
Robert H
RH
Neary
David
D
Snowden
Julie S
JS
Mann
David M A
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D006113:United Kingdom; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
C054369:MAPT protein, human; D025801:Ubiquitin; D016875:tau Proteins