New twin study informs our understanding of genetic vs modifiable risks for Alzheimer’s

Abnormal tau protein found in neurofibrillary tangles can be found in the brain at least several years before the onset of cognitive impairment in Alzheimer’s disease. Now a fascinating Dutch study of 78 cognitively normal, genetically identical twins (39 pairs), who all had evidence of brain amyloid in at least one of the pair when screened four years previously, and who carried at least one copy of the APOE-4 allele, looked at the amount and distribution of abnormal tau on their PET scans. The paper, published online ahead of print in Brain, is largely behind a paywall, but an accessible and excellent summary of the findings can be found on Alzforum, including a lovely group photo of the participants.

In all but seven of the twin pairs, the amount and distribution of tau in the brain was strikingly similar. Among the twins with discordant tau scans, most had been discordant for presence of amyloid on PET scans done four years before.  One explanation is that the discordant twins are simply on a different Alzheimer’s trajectory influenced by other factors.  Indeed, twins who were less physically or socially active, or who had more depressive symptoms, were more likely to have a greater burden of tau tangles than their siblings. This suggests that while our genes may determine regional vulnerability to tau accumulation, modifiable lifestyle factors may slow progression.