Genetic Background Responsible for Alzheimer’s Disease

Accumulation of amyloid plaque in the brain of Alzheimer’s disease vary among different groups of patients.

Genetic explanations for the differences between two commonly used brain imaging techniques for amyloid plaques have been identified by researchers at Karolinska Institutet in Sweden, published in the journal Molecular Psychiatry. This may help design more individual diagnostics and the development of future drugs.

Alzheimer’s disease (AD) is a neurodegenerative disease that leads to gradual memory loss and behavioral changes. It is characterized by the formation of beta-amyloid plaques and the tau proteins in the brain tissues, long before the actual symptoms occur. It affects almost 120,000 people in Sweden.

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‘Accumulation of amyloid plaque in the brain of Alzheimer’s disease vary among different groups of patients. This sheds light on different genetic differences among these patients that give rise to differing pathways. ’

According to Hjärnfonden, the number of AD cases will increase by 70 percent in 50 years, partly because we are living longer and longer.

Genetic differences in Alzheimer’s disease:

The PET camera and analysis of cerebrospinal fluid, CSF, from the spinal cord are reliable methods for detecting pathological accumulations of amyloid in the brain. However, divergence in results exists among 20 percent of cases at the early stages of the disease.

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The study among 867 participants with mild cognitive impairment, Alzheimer's dementia, and healthy controls were done using PET imaging and CSF analyses. Documentation of the amyloid accumulation was made for 2 years in a subset of nearly 300 participants.

This led to the identification of two alternative pathways for the development of amyloid pathology in Alzheimer's disease.

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The results thus show that pathological changes in some individuals are first detected in the brain with a PET camera, and in other individuals first with CSF analysis. In the latter group, the researchers also saw a higher incidence of Alzheimer's genetic risk factor and faster accumulation of amyloid plaques in the brain compared to the former group.

This sheds light on two different groups of patients, with different genetics and speed of amyloid plaque accumulation in the brain.

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"The differences in the results for biomarkers in the brain and CSF provide unique biological information and the opportunity for earlier and more individualized diagnosis and treatment for Alzheimer's disease in the future. The results may also be important for the design of clinical trials of new drugs against amyloid accumulation in the brain," says last author Elena Rodriguez-Vieitez, a senior researcher at the Department of Neurobiology, Caring Sciences, and Society, Karolinska Institutet.

Facts on Alzheimer's disease:

There are approximately 50 million people worldwide
More than 5 million Americans of all ages have Alzheimer's
An estimated 5.8 million Americans age 65 and older are living with Alzheimer's dementia in 2020
Eighty percent are age 75 or older
One in 10 people age 65 and older (10%) has Alzheimer's dementia