The gist of Alzheimer’s disease

By SWA

A detailed discussion about Alzheimer’s and Dementia disease by Robert Sapolsky - Father-Offspring Interviews and its broader context within human aging and brain health.
https://www.youtube.com/watch?v=zQGlunGu_v8&t=1054s

Here's a summary of the main points:

  1. What is Alzheimer's?

    • Alzheimer's is a type of dementia that affects specific types of memory. It does not entirely erase memory but primarily damages certain subtypes, like episodic and declarative memories, while sparing procedural memory (skills and habits).
    • Short-term memory, remote memory (like your native language from childhood), and procedural memory (how to do tasks) are often preserved, even in advanced stages.

  2. Types of Alzheimer's:

    • Early-Onset (Familial) Alzheimer's: Affects about 10% of cases, caused by specific genetic mutations, strikes people in their 50s, progresses rapidly, and is strongly heritable.
    • Late-Onset (Sporadic) Alzheimer's: The most common type, accounting for 90% of cases, with onset typically in the 70s or 80s. It progresses more slowly and involves a complex mix of genetic and lifestyle factors.

  3. Research and Controversy:

    • Research has been largely focused on amyloid plaques (protein clumps) and neurofibrillary tangles (twisted protein fibers), with debate between two camps: "BAP-tists" (focused on amyloid plaques) and "Tau-ists" (focused on tau tangles).
    • Treatments targeting these proteins, including antibodies to clear plaques, have largely failed to improve symptoms or halt progression, prompting skepticism about the direction of research.

  4. Genetics and Risk Factors:

    • Apolipoprotein E (ApoE): A gene with three main variants (E2, E3, E4) plays a significant role in modulating Alzheimer's risk, with E4 significantly increasing the risk and E2 reducing it.
    • Genetic predisposition accounts for only part of the risk; the rest is influenced by modifiable lifestyle factors.
    • APOE (OMIM 107741) ε4 carrier status TaqMan genotyping (rs7412 - 439 citations and rs429358 - 484 citations).

  5. Lifestyle Factors Affecting Alzheimer’s Risk:

    • About half of the risk for late-onset Alzheimer's is due to lifestyle factors, which are modifiable. These include:
      • Traumatic Brain Injury: Avoiding concussions and severe head trauma reduces risk.
      • Mental Health: Long-term untreated depression increases risk.
      • Sleep: Poor sleep hygiene can impede the brain’s ability to clear toxic proteins.
      • Vascular Health: Maintaining healthy blood vessels through diet, exercise, and avoiding smoking/alcohol abuse is crucial.
      • Physical Activity: Regular exercise improves cardiovascular health and provides direct benefits to brain cells.
      • Intellectual Stimulation: Lifelong learning, playing instruments, speaking new languages, and other forms of mental activity help keep the brain resilient.
      • Social Connections: Strong social ties and avoiding loneliness play a protective role in maintaining cognitive health.
      • Stress: Chronic stress may contribute to Alzheimer's pathology.

  6. Comparisons with Non-Human Primates:

    • Non-human primates do not get Alzheimer’s as humans do, although they do experience typical brain aging. Factors like different tau protein conformations and shorter lifespans may protect them from Alzheimer's.

  7. Evolutionary Hypotheses:

    • The evolution of human-specific variants of the ApoE gene (E2 and E3) suggests an adaptation for prolonged cognitive function, likely tied to the social and caregiving roles of grandmothers, which have significant survival benefits for human offspring.

  8. Broader Implications:

    • The passage emphasizes that while the scientific community has focused heavily on molecular aspects like amyloid plaques, the most promising areas may lie in understanding and modifying lifestyle and environmental factors.

This overview captures the complexities of Alzheimer's, the shortcomings of current research approaches, and the hope that modifiable lifestyle factors offer for reducing risk.

Reference: Alzheimer Disease Blood Biomarkers and Cognition Among Individuals With Diabetes and Overweight or Obesity 

Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer's disease risk
https://pubmed.ncbi.nlm.nih.gov/35809216/

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

 

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