Research ArticleNeurodegeneration

Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer’s disease

See allHide authors and affiliations

Science Signaling  10 May 2016:
Vol. 9, Issue 427, pp. ra47
DOI: 10.1126/scisignal.aaf6209

PKCα variants in Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by neurodegeneration and impaired neuronal function in the brain that lead to progressive cognitive loss. The early-onset form of AD is linked to genetic mutations, and accumulation of a protein called amyloid-β occurs in many patients with both early- and late-onset AD. By examining the genetics of a large cohort of families in which late-onset AD was diagnosed, Alfonso et al. found that activating mutations in protein kinase Cα (PKCα) correlated with the disease. Pharmacologically inhibiting PKCα or deleting the gene encoding it prevented amyloid-β from impairing synaptic activity in hippocampal tissue slices from mice. This study suggests that PKCα variants mediate the pathological effects of amyloid-β in some patients with late-onset AD.