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[O3–03–06]: 18 F‐AV‐1451 BINDING IN FAMILIAL FRONTOTEMPORAL LOBAR DEGENERATION WITH TAU PATHOLOGY
Author(s) -
Kreisl William Charles,
Cosentino Stephanie,
Cheran Gayathri,
Manoochehri Masood,
Cines Sarah,
Goldman Jill,
Huey Edward D.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.319
Subject(s) - frontotemporal lobar degeneration , tau protein , temporal cortex , asymptomatic carrier , frontotemporal dementia , asymptomatic , orbitofrontal cortex , tauopathy , pathology , corticobasal degeneration , temporal lobe , medicine , gene isoform , psychology , nuclear medicine , alzheimer's disease , neuroscience , progressive supranuclear palsy , biology , neurodegeneration , dementia , disease , gene , prefrontal cortex , genetics , cognition , epilepsy
Background: C9orf72 repeat-related disease is the most common cause of hereditary amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Similar to Alzheimer’s disease (AD), some C9orf72 expansion carriers who are cognitively impaired have been shown to have increases in tau neurofibrillary tangles at autopsy. Recently developed tau positron emission tomography (PET) imaging could potentially be an in vivo method to assess tau accumulation in C9orf72-related disease. We evaluated AV1451 PET as a diagnostic and prognostic biomarker for disease caused by C9orf72 repeat expansions. Methods: Eight C9orf72 expansion carriers (mean age: 63.4 6 4.1 years) and sixteen age and gender matched cognitively normal individuals (mean age: 63.6 6 5.0 years) underwent tau PET imaging. Regional AV1451 SUVR normalized to brainstem intensity from various brain regions was used to assess tau deposition between groups and corrected for multiple comparisons using a false discovery rate of 1%. Pearson correlation was used to evaluate tau deposition SUVR values and clinical characteristics including ALS-FRS (ALS functional ratting scale), disease duration, neuropsychiatric measures, as well as AD markers in CSF. Results: Symptomatic C9orf72 expansion carriers had an ALS-FRS of 26 6 10 (range 13-39), a disease duration of 2.59 6 1.16 years (range 1.21-4.19 years), and MMSE score of 27.0 6 3.1. Three quarters of the patients were symptomatic. C9orf72 expansion carriers had increased AV1451 uptake in the entorhinal cortex compared to a reference population of cognitively normal controls (C9: 1.0960.29, control: 0.7360.11, p1⁄40.0002). The entorhinal AV-1451 SUVR exceeds an a priori cutoff for tau deposition of 1.00 for brainstem-normalized values in 75% of C9orf72 subjects and in none of the controls. AV-1451 uptake within entorhinal, limbic, and cortical areas, corresponding to regional progression of tau pathology by Braak staging, did not correlate with clinical measures of severity (ALS-FRS and disease duration), neurocognitive performance defined by MMSE, executive, and visuospatial measures, or CSF markers of disease (Ab, total tau, and phospho-tau). Conclusions: C9orf72 expansion carriers exhibited increased AV-1451 uptake in entorhinal cortex compared to controls suggesting that tau