Alzheimer’s patients tend to have differed and increased genetic changes, says study

Errors present in DNA can get accumulated inside brain cells as one is aging. However, in patients with Alzheimer’s disease, these errors called somatic mutations may increase at a quicker rate.

Image Credit: Robert Kneschke/

Image Credit: Robert Kneschke/

A new study performed by investigators from Brigham and Women’s Hospital and Boston Children’s Hospital has discovered that patients with Alzheimer’s disease (AD) have a higher number of somatic mutations in their brain cells and that these mutations varied from people who did not have Alzheimer’s disease.

The outcomes of the team study have been reported in the journal Nature.

As we age, neurons are known to accumulate somatic mutations. In AD neurons, however, we see more mutations and DNA alterations. Our results suggest that AD neurons experience genomic damage that causes immense stress on cells and creates dysfunction among them. These findings may explain why many brain cells die during AD.”

Michael B. Miller, MD, PhD, Study Lead Author, Department of Pathology, Brigham and Women’s Hospital

With the help of single-cell whole-genome sequencing of 319 hippocampal and prefrontal cortex neurons of patients with or without AD, the researchers performed a study to identify the connection between the number and kind of somatic mutations and AD.

To gain better insight into the genomic changes that happened in AD neurons, scientists sequenced tissue DNA and found a bigger number of mutations called somatic single-nucleotide variants (sSNVs) in patients with AD.

Theorizing that a huge number of mutations have been caused due to increased DNA oxidation, researchers further quantified 8-Oxoguanine, known to be an indicator of oxidative stress and DNA damage, and also found that AD neurons were highly oxidized indeed.

Eventually, the breakthrough of housing DNA alterations in AD neurons offers scientists a window into cellular and molecular events taking place in AD pathogenesis.

Our findings suggest that the sheer number of oxidative lesions and somatic mutations we observed in AD neurons may contribute to its pathology.”

Michael B. Miller, MD, PhD, Study Lead Author, Department of Pathology, Brigham and Women’s Hospital

Two primary study limitations have been acknowledged by the study authors. Initially, two groups were majorly studied: patients having no neurologic disease and those with advanced AD based on the Braak staging system.

In the upcoming days, scientists are keen to study the neurons of individuals with intermediate-stage AD. Second, while single-cell, whole-genome sequencing was possible for the preliminary studies, the authors observe that there are sophisticated techniques enabling a detailed analysis of every strand of DNA that must be explored later.

In the future, we are eager to elucidate how the observed mutations in AD neurons cause neuronal cell death and are dedicated to aiding in the discovery of novel treatments that target these pathways.”

Michael B. Miller, MD, PhD, Study Lead Author, Department of Pathology, Brigham and Women’s Hospital

Journal reference:

Miller, M.B., et al. (2022) Somatic genomic changes in single Alzheimer’s disease neurons. Nature.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
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