Alzheimer’s as Type 3 Diabetes

There is a hypothesis that Alzheimer’s is a type of diabetes. If so, blood sugar regulation might be a treatment.

Alzheimer’s Disease Is Type 3 Diabetes–Evidence Reviewed

Suzanne M. de la Monte, M.D., M.P.H.1,2,3 and Jack R. Wands, M.D.3

Alzheimer’s disease (AD) has characteristic histopathological, molecular, and biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; dystrophic neurites; amyloid precursor protein, amyloid-β (APP-Aβ) deposits; increased activation of prodeath genes and signaling pathways; impaired energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA damage. Gaining a better understanding of AD pathogenesis will require a framework that mechanistically interlinks all these phenomena.

Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD; (2) extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD; (3) experimental brain diabetes produced by intracerebral administration of streptozotocin shares many features with AD, including cognitive impairment and disturbances in acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude that the term “type 3 diabetes” accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM.

Ok… so if insulin like growth factor is involved, could that be the mechanism by which excercize helps too?

Then just the idea that good blood glucose control is needed points a fat finger at sugar loaded diets in the “epidemic” of new cases. Perhaps we all just need more periodic fasts…

High-fat diet feeding for 16 weeks doubled mean body weight, caused T2DM, and marginally reduced mean brain weight.80 Those effects were associated with significantly increased levels of tau, IGF-1 receptor, IRS-1, IRS-4, ubiquitin, glial fibrillary acidic protein (GFAP), and 4-hydroxynonenal and decreased expression of β actin. Importantly, HFD feeding also caused brain insulin resistance manifested by reduced top-level (Bmax) insulin receptor binding and modestly increased brain insulin gene expression. However, HFD fed mouse brains did not exhibit AD histopathology or increases in APP-Aβ or phospho-tau, nor were there impairments in IGF signaling, which typically occurs in AD.10 In essence, although the chronic obesity with T2DM model exhibited mild brain atrophy with insulin resistance, oxidative stress, and cytoskeleton degradation, the effects were modest compared with AD5,10 and other more robust experimental models of T3DM,28,29 and most of the molecular, biochemical, and histopathological features that typify AD were not present. Therefore, T2DM and obesity may contribute to, i.e., serve as cofactors of AD but by themselves are probably not sufficient to cause AD.

Yeah, fat rats don’t think as well, got it…. (where did I put that bike in the garage…)

There is much more in the article, well woth reading it. Human studies, drugs that work, and more.

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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
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3 Responses to Alzheimer’s as Type 3 Diabetes

  1. H.R. says:

    Excellent post, E.M. You are “onto something” here.

    I was diagnosed with Type II diabetes in January of this year. I didn’t see that coming. I just got a letter from my Dr. letting me know that my A1C (avg. blood sugar) was at our goal for me. Yay!

    I have noticed the link between insulin resistance and memory in my personal experience and some observations of my mom (see my note on August Tips thread).

    I’ll be tied up for a week or so, but I will post more details here in support of Alzheimer’s being “Type III” diabetes when I get a chance.

  2. pohakea says:

    The most wonderful site, intensivedietarymanagement dot com, T2D post 40 from 19 July 2017, has answers. I got to there thanks to fastingtalk dot com, podcast episode 18: “fatty liver” (mp3)
    I wish to pass along a citation, also ncbi dot nlm dot nih dot gov/pmc/articles/PMC2880185/ (2010),
    “… gluttony” and “sloth” (overnutrition and underexertion), the cardinal causes of the metabolic syndrome … The lethal consequences of co-morbidities of obesity can actually be “Darwinized” to explain the evolution of genes such as proprotein convertase subtilin/kexin type 9 (PCSK9), the only known function of which is to degrade the LDL receptor and thereby increase LDL-cholesterol [1] in individuals who consume an atherogenic diet. If its only function is to increase risk of heart disease, could this signify that collective survival is protected at the expense of individual survival? Could elimination of gluttonous and slothful members of a society after their reproductive years assure the youngest members of the group a fair share of food during times of limited supply? …”
    In GundryMD dot com “Diet Evolution,” the “killer genes” activate by poor diet and over exertion.
    “The wrath of God came upon them, and slew the fattest …” (suffering them to be surfeited by excessive eating) 78th Psalm, Verse 31 … plump quail, blown ashore: Darwinized, all! Oh, my!

  3. Pingback: T2 Diabetes – Hibernation Lite? | Musings from the Chiefio

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