Alzheimer’s biomarkers present decades before symptoms

July, 2012
  • People with a strong genetic risk of early-onset Alzheimer’s have revealed a progression of brain changes that begin 25 years before symptoms are evident.

A study involving those with a strong genetic risk of developing Alzheimer’s has found that the first signs of the disease can be detected 25 years before symptoms are evident. Whether this is also true of those who develop the disease without having such a strong genetic predisposition is not yet known.

The study involved 128 individuals with a 50% chance of inheriting one of three mutations that are certain to cause Alzheimer’s, often at an unusually young age. On the basis of participants’ parents’ medical history, an estimate of age of onset was calculated.

The first observable brain marker was a drop in cerebrospinal fluid levels of amyloid-beta proteins, and this could be detected 25 years before the anticipated age of onset. Amyloid plaques in the precuneus became visible on brain scans 15-20 years before memory problems become apparent; elevated cerebrospinal fluid levels of the tau protein 10-15 years, and brain atrophy in the hippocampus 15 years. Ten years before symptoms, the precuneus showed reduced use of glucose, and slight impairments in episodic memory (as measured in the delayed-recall part of the Wechsler’s Logical Memory subtest) were detectable. Global cognitive impairment (measured by the MMSE and the Clinical Dementia Rating scale) was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.

Family members without the risky genes showed none of these changes.

The risky genes are PSEN1 (present in 70 participants), PSEN2 (11), and APP (7) — note that together these account for 30-50% of early-onset familial Alzheimer’s, although only 0.5% of Alzheimer’s in general. The ‘Alzheimer’s gene’ APOe4 (which is a risk factor for sporadic, not familial, Alzheimer’s), was no more likely to be present in these carriers (25%) than noncarriers (22%), and there were no gender differences. The average parental age of symptom onset was 46 (note that this pushes back the first biomarker to 21! Can we speculate a connection to noncarriers having significantly more education than carriers — 15 years vs 13.9?).

The results paint a clear picture of how Alzheimer’s progresses, at least in this particular pathway. First come increases in the amyloid-beta protein, followed by amyloid pathology, tau pathology, brain atrophy, and decreased glucose metabolism. Following this biological cascade, cognitive impairment ensues.

The degree to which these findings apply to the far more common sporadic Alzheimer’s is not known, but evidence from other research is consistent with this progression.

It must be noted, however, that the findings are based on cross-sectional data — that is, pieced together from individuals at different ages and stages. A longitudinal study is needed to confirm.

The findings do suggest the importance of targeting the first step in the cascade — the over-production of amyloid-beta — at a very early stage.

Researchers encourage people with a family history of multiple generations of Alzheimer’s diagnosed before age 55 to register at http://www.DIANXR.org/, if they would like to be considered for inclusion in any research.

Reference: 

[2997] Bateman, R. J., Xiong C., Benzinger T. L. S., Fagan A. M., Goate A., Fox N. C., et al.
(2012).  Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease.
New England Journal of Medicine. 120723122607004 - 120723122607004.

Related News

A study involving more than 2,500 older adults (65+) found that the rate of worsening vision was associated with the rate of cognitive decline. More importantly, vision has a stronger influence on cognition than the reverse.

Hearing loss linked to increased dementia risk

Chronic insomnia linked to memory problems

Link found between chronic inflammation and Alzheimer's gene risk

Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less

A large Chinese study involving 20,000 people has found that the longer people were exposed to air pollution, the worse their cognitive performance in verbal and math tests. The effect of air pollution on verbal tests became more pronounced with age, especially for men and the less educated.

A review of 34 longitudinal studies, involving 71,244 older adults, has concluded that depression is associated with greater cognitive decline.

A study following nearly 28,000 older men for 20 years has found that regular consumption of leafy greens, dark orange and red vegetables and berry fruits, and orange juice, was associated with a lower risk of memory loss.

Poor sleep has been associated with the development of Alzheimer's disease, and this has been thought to be in part because the protein amyloid beta increases with sleep deprivation. A new study explains more.

A small study has found that a 12-week exercise program significantly improved cognition in both older adults with

Pages

Subscribe to Latest newsSubscribe to Latest newsSubscribe to Latest health newsSubscribe to Latest news
Error | About memory

Error

The website encountered an unexpected error. Please try again later.