Progranulin Mutations as Risk Factors for Alzheimer Disease

JAMA neurology 04/2013; 70(6):1-5. DOI: 10.1001/2013.jamaneurol.393
Source: PubMed


Mutations in the progranulin gene are known to cause diverse clinical syndromes, all attributed to frontotemporal lobar degeneration. We describe 2 patients with progranulin gene mutations and evidence of Alzheimer disease (AD) pathology. We also conducted a literature review.

This study focused on case reports of 2 unrelated patients with progranulin mutations at the University of California, San Francisco, Memory and Aging Center. One patient presented at age 65 years with a clinical syndrome suggestive of AD and showed evidence of amyloid aggregation on positron emission tomography. Another patient presented at age 54 years with logopenic progressive aphasia and, at autopsy, showed both frontotemporal lobar degeneration with TDP-43 inclusions and AD.

Conclusions and relevance:
In addition to autosomal-dominant frontotemporal lobar degeneration, mutations in the progranulin gene may be a risk factor for AD clinical phenotypes and neuropathology.

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Available from: Jennifer S Yokoyama, Aug 27, 2014
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    • "Loss of function mutations in the GRN gene are related to pro-inflammatory cytokine dysregulation in FTLD patients [18]. In addition, mutations in GRN are also associated with increased prevalence of specific and related autoimmune diseases, including inflammatory arthritis [19] [20]. PGRN binding receptors and signaling in mediating its antiinflammatory functions in neurons still remain elusive. "
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    FEBS letters 09/2013; 59(21). DOI:10.1016/j.febslet.2013.09.024 · 3.17 Impact Factor
  • 04/2013; 70(6):1-2. DOI:10.1001/jamaneurol.2013.2854
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    ABSTRACT: Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor-like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. We review here progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight the growth factor-like, trophic, and anti-inflammatory properties of progranulin as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment.
    Trends in Endocrinology and Metabolism 09/2013; 24(12). DOI:10.1016/j.tem.2013.08.003 · 9.39 Impact Factor
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