UCL Institute of Neurology

Younger brains better than old in clearing Alzheimer’s-related protein, study finds. Younger brains are more effective than older brains at getting rid of abnormal amounts of tau protein associated with Alzheimer’s disease – a mechanism that may be partly explained by a better stress response in the young, a mouse-model study led by researchers at the University of South Florida found.

The study, published this month in the American Journal of Pathology, also suggests that once some abnormal tau is produced in the brain it may interfere with the normal turnover of tau protein and lead to its destructive buildup. While normal tau helps maintain the structure of neurons, the excessive accumulation of tau leads to fibrous Alzheimer’s tangles that choke the brain’s memory center.

Co-author, Dr Rohan de Silva (Reta Lila Weston Institute) explains the basis of the IoN research:

" The accumulation of abnormal aggregates of tau (tangles) is a feature not only of the Alzheimer's disease brain but also in the other "tauopathies" which include the parkinsonian disorder, progressive supranuclear palsy (PSP).

This study shows that a small amount of abnormal tau can act as a "seed" for facilitating the conversion of normal tau, leading to functional impairment and accumulation.

In the normal human brain, tau is present as 6 closely related variants and each of these variants may have a distinct function. There is increasing evidence that the composition of tau related to these six variants is finely balanced and that subtle changes in one or more of these variants can cause damage and death of specific neuronal populations. In our lab, we have shown that even without overt mutational defects in the tau protein, common genetic variation in the tau gene can cause such subtle changes in the levels and ratios of the 6 tau variants and increase risk of PSP. The findings in this paper show that the presence or excess of one defective variant of tau could impair clearance of "normal" tau thereby inducing a cascade of deleterious changes."