Drs. Simon D’Alton & Jada Lewis publish in Oct 2014 Nature Medicine

“Understanding the role of progranulin in Alzheimer’s disease.”
D’Alton S, Lewis J.  Nat Med 2014; 20(10):1099-1100.
PMID: 25295938


Alzheimer’s disease is characterized by severe cognitive decline and brain amyloid plaques. A new study in mouse models that develop features of Alzheimer’s disease indicates that progranulin may have a role in clearing these plaques.

Alzheimer’s disease (AD) is a neurodegenerative disease projected to affect up to 13.8 million people in the US by 2050 (ref. 1). Most current therapeutic efforts have been designed to target amyloid-β, a protein that aggregates into ‘plaques’ in the Alzheimer’s disease brain; however, recent disappointing clinical trial results have triggered interest in indirect or alternative strategies2. In a different neurodegenerative disease termed frontotemporal lobar degeneration (FTLD), mutations in the granulin (GRN) gene lead to haploinsufficiency of progranulin protein and neurodegeneration3, 4. Progranulin is a secreted protein expressed in the brain by microglia and neurons. It has a role in both neurotrophic and inflammatory processes, and there has been growing optimism that increasing the level of progranulin might be an effective treatment for FTLD5. Prior work has also linked GRN polymorphisms to an increased risk of AD6; therefore, therapeutics for FTLD could potentially provide a therapeutic strategy for AD, as well.