Abstract Frontotemporal lobar degeneration (FTLD) encompasses a heterogeneous group of clinical syndromes that include frontotemporal
dementia (FTD), frontotemporal dementia with motor neurone disease (FTD/MND), progressive non-fluent aphasia (PNFA), semantic
dementia (SD) and progressive apraxia (PAX). Clinical phenotype is often assumed to be a poor predictor of underlying histopathology.
Advances in immunohistochemistry provide the opportunity to re-examine this assumption. We classified pathological material
from 79 FTLD brains, blind to clinical diagnosis, according to topography of brain atrophy and immunohistochemical characteristics.
There were highly significant relationships to clinical syndrome. Atrophy was predominantly frontal and anterior temporal
in FTD, frontal in FTD/MND, markedly asymmetric perisylvian in PNFA, asymmetric bitemporal in SD and premotor, parietal in
PAX. Tau pathology was found in half of FTD and all PAX cases but in no FTD/MND or SD cases and only rarely in PNFA. FTD/MND,
SD and PNFA cases were ubiquitin and TDP-43 positive. SD cases were associated with dystrophic neurites without neuronal cytoplasmic
or intranuclear inclusions (FTLD-U, type 1), FTD/MND with numerous neuronal cytoplasmic inclusions (FTLD-U, type 2 ) and PNFA
with neuronal cytoplasmic inclusions, dystrophic neurites and neuronal intranuclear inclusions (FTLD-U, type 3). MAPT mutations were linked to FTD and PGRN mutations to FTD and PNFA. The findings demonstrate predictable relationships between clinical phenotype and both topographical
distribution of brain atrophy and immunohistochemical characteristics. The findings emphasise the importance of refined delineation
of both clinical and pathological phenotype in furthering understanding of FTLD and its molecular substrate.
Content TypeJournal Article
JournalActa NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica)
Tags: Disability and special needs by Operative Techniques in Orthopaedics
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