Dataset Information

Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.

ABSTRACT:

Objective

Predictable patterns of atrophy are associated with the clinical subtypes of frontotemporal dementia (FTD): behavioral variant (bvFTD), semantic dementia (SEMD), and progressive nonfluent aphasia (PNFA). Some studies of pathologic subtypes have also suggested specific atrophy patterns; however, results are inconsistent. Our aim was to test the hypothesis that clinical, but not pathologic, classification (FTD with ubiquitin inclusions [FTD-U] and FTD with tau inclusions [FTD-T]) is associated with predictable patterns of regional atrophy.

Methods

Magnetic resonance scans of nine FTD-U and six FTD-T patients (histologically confirmed) were compared with 25 controls using voxel-based morphometry (VBM). Analyses were conducted with the patient group classified according to histologic or clinical variant. Additionally, three Alzheimer pathology patients who had the syndrome of SEMD in life (FTD-A) were analyzed.

Results

The VBM studies in clinical variants confirmed established patterns of atrophy (SEMD, rostral temporal; bvFTD, mesial frontal; PNFA, left insula). FTD-U and FTD-T VBM results were very similar, showing severe atrophy in the temporal poles, mesial frontal lobe, and insulae. A conjunction analysis confirmed this similarity. Subgroup analysis found that SEMD associated with either FTD-T or FTD-U was associated with similar rostral temporal atrophy; however, FTD-A had a qualitatively different pattern of left hippocampal atrophy.

Conclusions

While there is predictable atrophy for clinical variants of frontotemporal dementia (FTD), histologic FTD variants show no noticeable differences. Reports of specific atrophy profiles are likely the result of idiosyncrasies in small groups. Semantic dementia associated with Alzheimer pathology, however, presented a distinct atrophy pattern.

SUBMITTER: Pereira JM

PROVIDER: S-EPMC2827263 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.

Pereira J M S JM Williams G B GB Acosta-Cabronero J J Pengas G G Spillantini M G MG Xuereb J H JH Hodges J R JR Nestor P J PJ

Neurology 20090501 19

<h4>Objective</h4>Predictable patterns of atrophy are associated with the clinical subtypes of frontotemporal dementia (FTD): behavioral variant (bvFTD), semantic dementia (SEMD), and progressive nonfluent aphasia (PNFA). Some studies of pathologic subtypes have also suggested specific atrophy patterns; however, results are inconsistent. Our aim was to test the hypothesis that clinical, but not pathologic, classification (FTD with ubiquitin inclusions [FTD-U] and FTD with tau inclusions [FTD-T]) ...[more]

PMID: 19433738

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Project description:BACKGROUND:Microglial dysfunction is implicated in frontotemporal lobar degeneration (FTLD). Although studies have reported excessive microglial activation or senescence (dystrophy) in Alzheimer's disease (AD), few have explored this in FTLD. We examined regional patterns of microglial burden, activation and dystrophy in sporadic and genetic FTLD, sporadic AD and controls. METHODS:Immunohistochemistry was performed in frontal and temporal grey and white matter from 50 pathologically confirmed FTLD cases (31 sporadic, 19 genetic: 20 FTLD-tau, 26 FTLD-TDP, four FTLD-FUS), five AD cases and five controls, using markers to detect phagocytic (CD68-positive) and antigen-presenting (CR3/43-positive) microglia, and microglia in general (Iba1-positive). Microglial burden and activation (morphology) were assessed quantitatively for each microglial phenotype. Iba1-positive microglia were assessed semi-quantitatively for dystrophy severity and qualitatively for rod-shaped and hypertrophic morphology. Microglia were compared in each region between FTLD, AD and controls, and between different pathological subtypes of FTLD, including its main subtypes (FTLD-tau, FTLD-TDP, FTLD-FUS), and subtypes of FTLD-tau, FTLD-TDP and genetic FTLD. Microglia were also compared between grey and white matter within each lobe for each group. RESULTS:There was a higher burden of phagocytic and antigen-presenting microglia in FTLD and AD cases than controls, but activation was often not increased. Burden was generally higher in white matter than grey matter, but activation was greater in grey matter. However, microglia varied regionally according to FTLD subtype and disease mechanism. Dystrophy was more severe in FTLD and AD than controls, and more severe in white than grey matter, but this also varied regionally and was particularly extensive in FTLD due to progranulin (GRN) mutations. Presence of rod-shaped and hypertrophic microglia also varied by FTLD subtype. CONCLUSIONS:This study demonstrates regionally variable microglial involvement in FTLD and links this to underlying disease mechanisms. This supports investigation of microglial dysfunction in disease models and consideration of anti-senescence therapies in clinical trials.

Dataset Information

Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.

Objective

Methods

Results

Conclusions

Publications

Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.

Similar Datasets

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