(HealthDay News) – Rare variants of three genes linked to early-onset Alzheimer’s disease can also be found in individuals with late-onset Alzheimer’s disease, suggesting that mutations are not the only factor affecting age of onset, according to a study published online Feb. 1 in PloS One.
Carlos Cruchaga, Ph.D., from Washington University in St. Louis, and colleagues sequenced the APP, PSEN1, PSEN2, MAPT, and GRN genes in 439 families in which four or more members had been diagnosed with late-onset Alzheimer’s disease. APP, PSEN1, and PSEN2 have been linked to early-onset Alzheimer’s disease, while MAPT and GRN have been associated with familial frontotemporal dementia.
The researchers identified 33 novel or pathogenic variants in 60 individuals (13.7%). Eight pathogenic variants (one in APP, one in MAPT, two in PSEN1, and four in GRN), of which three were novel, were identified in fourteen individuals. Thirteen variants, of which eight were novel, were found in 23 families. Although these did not segregate with disease, they were more common in patients with Alzheimer’s disease.
“Rare coding variants in APP, PSEN1, and PSEN2, increase risk for or cause late-onset Alzheimer’s disease. The presence of variants in these genes in late-onset Alzheimer’s disease and early-onset Alzheimer’s disease demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with Alzheimer’s disease,” Cruchaga and colleagues conclude. “MAPT and GRN mutations can be found in clinical series of Alzheimer’s disease most likely due to misdiagnosis.”
Several authors are employees of GlaxoSmithKline.