According to new research, Alzheimer’s appears to occur in two stages: a slow, symptomless phase that affects only a few susceptible cell types and a destructive later phase that manifests the disease’s hallmark signs and symptoms. The results could aid scientists in creating novel approaches to early Alzheimer’s diagnosis and treatment.
Alzheimer’s disease is the most prevalent type of dementia, a degenerative neurological condition that eventually interferes with day-to-day activities by affecting memory, thinking, and behavior.
The World Health Organization (WHO) estimates that 10 million individuals worldwide receive a dementia diagnosis each year and that approximately 55 million people worldwide are living with dementia [1]. Up to 70% of these individuals have Alzheimer’s.
Mild memory loss is typically the initial sign of Alzheimer’s, and as time passes, the symptoms worsen. Later-stage Alzheimer’s patients frequently require 24-hour care since they are unable to carry out ordinary daily tasks and have conversations.
Changes in the brain trigger the disease symptoms. However, a new study indicates that some brain changes may begin long before symptoms appear.
The National Institutes of Health (NIH)-funded study contends that Alzheimer’s first slow and silent phase arises before any memory loss, damaging only a few susceptible brain cells. Plaques, tangles, and other markers of Alzheimer’s accumulate during the second phase, which is more destructive and occurs when symptoms start to appear.
Nature Neuroscience published the research [2].
Alzheimer’s First Phase: Slow, Early Changes in Brain
The research team examined brains from 84 donors (postmortem), with an average age of 88. There were 51 female and 33 male donors; 9 of them had no Alzheimer’s, 12 had low ADNC (Alzheimer’s disease neuropathological changes), 21 had intermediate ADNC, and 42 had high ADNC.
About one-third of intermediate (7 of 21) and low (4 of 12) ADNC cases and nearly three-quarters (31 of 42) of high ADNC cases had dementia before death. Before passing away, none of the people without ADNC developed dementia.
For each donor, the researchers first employed machine learning to measure Alzheimer’s progression, including beta-amyloid and pTau, which indicate the amount of phosphorylated tau protein in blood plasma.
Each received a score ranging from 0 to 1. The researchers discovered that a score of 0.4-0.6 indicated a significant rise in pTau and beta-amyloid buildup and increased cognitive impairments.
They concluded from the scores that there are two distinct phases that characterize the severity of Alzheimer’s:
In an NIH news release, Richard J. Hodes, MD, director of the NIH National Institute on Aging, stated that an obstacle to identifying and treating Alzheimer’s disease is that a large portion of brain damage occurs long before symptoms appear [3].
He went on to say that by being able to identify these early changes, we can finally observe what is happening to a person’s brain in the early stages of the illness.
Early Cell Damage Causes Subsequent Changes in the Brain.
The researchers were surprised to discover that, accompanied by a gradual buildup of plaques and immune system activity in the brain, one specific kind of neuron, or nerve cell, was dying.
Somatostatin (SST) inhibitory neurons typically transmit soothing signals to other cells. The death of these neurons may set off the ensuing modifications in the brain that drive Alzheimer’s, according to the study’s authors.
The researchers point out that inhibitory neurons might be one of the first brain cell types to become susceptible and cause changes in intercellular communication. These cells are predominantly present in a brain area related to memory, vision, and language.
Alzheimer’s Second Phase: Inflammable and Increased Damage
The researchers reported a decrease in oligodendrocytes and an increase in inflammatory cells known as astrocytes and microglia after the loss of SST inhibitory neurons.
Oligodendrocytes create myelin, the nerve cell’s outer coating that is necessary for nerve impulse transmission.
Researchers suggest that other inflammatory brain cells, known as microglia and astrocytes, start a process to try to reverse these early alterations by releasing chemicals or altering their structure in what they refer to as the later phase of the disease [4].
Changes in inflammatory cells and inhibitory neurons gradually evolve to display the well-known molecular abnormalities of Alzheimer’s, including amyloid plaque deposition and tau tangle pathology, resulting in a deadly state.
Could these findings contribute to early Alzheimer’s diagnosis?
Researchers were able to identify the initial cellular alterations in the brain as Alzheimer’s progressed via powerful new technology. According to the study’s authors, their research could result in novel treatments and diagnostics focusing on particular disease phases.
Alzheimer’s Research Association is a non-profit organization dedicated to helping caregivers of Alzheimer’s disease and dementia. We provide the latest information and news about the illness and helpful tips to help caregivers cope with their daily caregiving challenges. We realize the most important thing that a caregiver needs is financial assistance. Therefore, we provide grants to caregivers to ease their financial burden. Caregivers can apply for grants here: Alzheimer’s Grant Application.
You can also help caregivers in their endeavor by donating as much as possible: Donation To Alzheimer’s Research Associations.
References
- Dementia. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/dementia. Published Online: 15thmarch, 2023. Accessed: 22nd November, 2024.
- Gabitto, M.I., Travaglini, K.J., Rachleff, V.M., Kaplan, E.S., Long, B., Ariza, J., Ding, Y., Mahoney, J.T., Dee, N., Goldy, J. and Melief, E.J., 2024. Integrated multimodal cell atlas of Alzheimer’s disease. Nature Neuroscience, pp.1-18.
- Alzheimer’s disease may damage the brain in two phases. News Release. National Institutes of Health. https://www.nih.gov/news-events/news-releases/alzheimer-s-disease-may-damage-brain-two-phases. Published Online: 15th October, 2024. Accessed: 22nd November, 2024.
- Study detects early Alzheimer’s ‘stealth’ phase before symptoms set in. Medical News Daily. https://www.medicalnewstoday.com/articles/study-detects-early-alzheimers-stealth-phase-before-symptoms-set-in. Published Online: 21st October, 2024. Accessed: 22nd November, 2024.
- Alzheimer’s Disease Harms The Brain in 2 Distinct Phases, Study Reveals. Science Alert. https://www.sciencealert.com/alzheimers-disease-harms-the-brain-in-2-distinct-phases-study-reveals. Published Online: 17th October, 2024. Accessed: 22nd November, 2024.
- New study reveals Alzheimer’s disease progresses in two distinct phases. Touch Neurology. https://touchneurology.com/insight/new-study-reveals-alzheimers-disease-progresses-in-two-distinct-phases/. Published Online: 22nd October, 2024. Accessed: 22nd November, 2024.
