Blocking inflammation receptor helps Alzheimer's mice

Low levels of DHA, an omega-3 fatty acid, have been found in the brains of those with Alzheimer's disease, but the reason has not been known. A new study has found that lower levels of DHA in the liver (where most brain DHA is manufactured) were correlated with greater cognitive problems in the Alzheimer’s patients. Moreover, comparison of postmortem livers from Alzheimer’s patients and controls found reduced expression of a protein that converts a precursor acid into DHA, meaning the liver was less able to make DHA from food.

While everyone agrees that amyloid-beta protein is part of the problem, not everyone agrees that amyloid plaques are the cause (or one of them) of Alzheimer’s. Other forms of amyloid-beta have been pointed to, including floating clumps called oligomers or ADDLs. A new study, using mice engineered to form only these oligomers, and never any plaques, throughout their lives, provides more support for this theory.

It’s been suggested before that Down syndrome and Alzheimer's are connected. Similarly, there has been evidence for connections between diabetes and Alzheimer’s, and cardiovascular disease and Alzheimer’s. Now new evidence shows that all of these share a common disease mechanism. According to animal and cell-culture studies, it seems all Alzheimer's disease patients harbor some cells with three copies of chromosome 21, known as trisomy 21, instead of the usual two. Trisomy 21 is characteristic of all the cells in people with Down syndrome.

A two-year study which involved metabolic testing of 50 people, suggests that Alzheimer's disease consists of three distinct subtypes, each one of which may need to be treated differently. The finding may help explain why it has been so hard to find effective treatments for the disease.

The subtypes are:

New findings identify a mechanism that accelerates aging in the brain and gives rise to Alzheimer's disease.

The findings center on “enhancers”, which turn the activity of genes up or down based on influences like aging and environmental factors. Comparing enhancers in brain cells of people at varying stages of Alzheimer's and healthy people has revealed that in normal aging, there is a progressive loss of important epigenetic marks on enhancers. This loss is accelerated in the brains of people with Alzheimer's.

A very long-running study involving 290 people at risk of Alzheimer's has found that, in those 81 people who developed MCI or dementia, subtle changes in cognitive test scores were evident 11 to 15 years before the onset of clear cognitive impairment. They also showed increases in the rate of change of tau protein in cerebrospinal fluid an average of 34.4 years (for t-tau, or total Tau) and 13 years (for a modified version called p-tau) before the beginning of cognitive impairment.