Journal
NEUROLOGY
Volume 75, Issue 23, Pages 2079-2086Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e318200d78d
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Funding
- Penn-Pfizer Alliance
- NIH [AG-10124, AG-17586, NS-44266, AG17586, AG15116, NS53488, NS44266, NIA P01 AG 09215-20, NIA P30 AG 10124-18, NIA PO1 AG 17586-10, NIA 1PO1 AG-19724-07, NIA 1 U01 AG 024904-05, NINDS P50 NS053488-02, NIA UO1 AG029213-01, RC2NS069368, RC1AG035427, NIA P30AG036468]
- American Academy of Neurology Foundation
- Burroughs Wellcome Fund
- American Academy of Neurology
- Eli Lilly and Company
- Pfizer Inc
- Elan Corporation
- Wyeth
- Janssen
- Marian S. Ware Family Foundation
- Department of Health, Commonwealth of Pennsylvania
- NIH [Co-PI Biomarker Core Laboratory] [AG024904]
- NIH [ARRA] [PI Biomarker Core Laboratory] [1RC 2AG-036535]
- ALS Association
- Muscular Dystrophy Association
- Teva Pharmaceutical Industries Ltd.
- Boehringer Ingelheim
- Bayer Schering Pharma
- Kyowa Hakko Kirin Pharma, Inc.
- PRA International, Novartis
- GlaxoSmithKline
- Avid Radiopharmaceuticals, Inc.
- St Jude Medical
- Amarin Corporation
- Prestwick Pharmaceutical, Inc.
- HP Therapeutics Foundation, Inc.
- Cephalon, Inc.
- NIH (NINDS) [P50 NS053488-01, U10 NS044451-023, U10 NS0444451, P50 NS053488, R43NS0636071, R01NS065087]
- US Department of Defense
- Department of Health
- Commonwealth of Pennsylvania
- Takeda Pharmaceutical Company Limited
- Genentech, Inc.
- Marian S. Ware Alzheimer Program
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Objective: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau). Methods: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD. Results: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases. Conclusions: Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF. Neurology (R) 2010;75:2079-2086
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