Alzheimer's disease can affect the brain in phases

Press release

Tuesday October 15, 2024

NIH-funded brain mapping study reveals which cell types are most likely to be damaged first.

According to a new study funded by the National Institutes of Health, Alzheimer's disease may affect the brain at two different stages. The research was conducted using advanced brain mapping techniques. The researchers who came up with this new insight believe that the early stage occurs slowly, silently, before memory problems arise, and affects only a small number of vulnerable cells. The second phase, which is the late stage, causes more widespread damage and occurs in conjunction with symptoms, plaques and tangles.

The fact that symptoms of Alzheimer's disease often appear before actual damage is done to the brain makes it difficult to diagnose and treat. Dr. Richard J. Hodes is the director of the National Institute on Aging at the NIH. He said the ability to detect early changes allows us to see the state of the brain during the early stages of Alzheimer's disease. The findings will change the way scientists understand how Alzheimer's affects the brain and guide new treatment options for this debilitating disease.

The results of the analysis were published in Nature NeuroscienceThe study suggests that the problems in neural circuits that drive the disease may be caused by damage to a certain type of cell called an inhibitory neuromon during the early stages. The study also confirmed previous findings about how Alzheimer's disease affects the brain and identified many changes that may occur during the disease.

The scientists studied cells in the middle temporal cortex, an area of the brain that controls memory, language, and vision. The gyrus has been shown to be vulnerable to many of the changes seen in Alzheimer's disease. The researchers also extensively mapped this part of the human brain for control donors. The scientists created a timeline of Alzheimer's disease by comparing data from control donors with data from patients with the disease.

In the past, researchers thought that Alzheimer's disease occurred in stages, with increased cell death and inflammation, and a buildup of proteins in plaques and tangles. However, this study suggests that Alzheimer's disease affects the brain in two phases or "epochs," with the majority of changes occurring rapidly in the second phase. Memory problems and other symptoms are also present.

The findings also indicate that the first changes occur "quietly and gradually" during the initial phase, before symptoms are visible. The changes include a slow buildup of plaques in the brain, activation of its immune system, damage to the cellular insulation that helps send messages to neurons, and the death of cells known as somatostatin inhibitory neurons (SINs).

The researchers were surprised by the latest finding. Scientists traditionally thought that Alzheimer's disease was caused primarily by damage to excitatory neuron cells, which transmit activation signals. The inhibitory neuron sends calming messages to other cells. The study authors hypothesized that the loss of SST inhibitory neurons could trigger changes in the brain's neural circuits that are at the root of the disease.

Recent NIH-funded brain mapping research has been conducted separately. MIT researchers conducted a study Researchers have discovered that the REELIN gene may be linked to some neuronal vulnerability to Alzheimer's disease. The study also revealed that star-shaped brain cells called astrocytes may provide resistance to the effects of the disease.

Scientists analyzed the brains of the chimpanzee population. The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD), aimed to create a detailed map of brain damage during the disease. Mariano I. Gabitto and Kyle J. Travaglini of the Allen Institute in Seattle led this project. The scientists used tools developed by the researchers in this project. Brain Research Initiative through the Advancement of Innovative Neurotechnologies (r) from NIH (BRAIN). – Cell Census Network The study will involve more than 3.4 million brain cells taken from deceased donors at various stages of Alzheimer's disease. The tissue samples come from the study The Changes of Adult Thought and of Alzheimer's Disease Research Center from the University of Washington.This research shows how the NIH BRAIN Initiative’s powerful technologies are changing our understanding of diseases like Alzheimer’s. These tools have allowed scientists to identify early cellular changes in the brain, giving them a comprehensive picture of the disease’s progression. John Ngai, Ph.D., is director of the BRAIN Initiative. The new information provided by the study could help drug and diagnostic developers develop treatments and diagnostics specific to Alzheimer’s and other forms of dementia.

The NIH funded this study:

U19AG060909 ,P30AG066509 ,U19AG066567 ,U01AG006781 . The Nancy and Buster Alvord Endowment provided additional funding. Rush University Alzheimer's Disease Center in Chicago, Illinois, shared donor metadata for the Religious Orders Memory/Memory and Aging Project.The SEA-AD website contains data that researchers can access.

https://portal.brain-map.org/explore/seattle-alzheimers-disease The National Institute on Aging

The NIA is the lead agency in the U.S. federal government for conducting and supporting research related to aging and the health and well-being of older adults. The NIA provides a wealth of information on age-related changes in cognition and neurodegenerative diseases.Alzheimer's and Related Dementias Education and Referral Center (ADEAR) website. . You can find information on a wide range of topics related to aging on the NIA's main website.English You can also learn more about the following: Spanish “ Stay connected .The BRAIN Initiative

A multidisciplinary collaboration betweenTen NIH Institutes and Centers The BRAIN(r) Initiative is uniquely positioned to make cross-cutting discoveries in neuroscience that will revolutionize how we understand the brain. The BRAIN(r) Initiative accelerates the development and use of neurotechnologies to enable researchers to gain unprecedented insights into the brain in health and disease. This will improve how we prevent and treat brain disorders. The BRAIN Initiative is a network of multidisciplinary federal and non-federal partners whose current research portfolios and missions complement the goals of the BRAIN Initiative.The National Institutes of Health:

The NIH is the medical research agency of the U.S. Department of Health and Human Services. It includes 27 institutes and centers. The NIH, the nation's medical research agency, is a component of the U.S. Department of Health and Human Services. It is responsible for conducting basic, translational, clinical, and other medical research. Visit the NIH website for more information about its programs. www.nih.gov .NIH…Transforming Discovery into Healthcare

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