Thread by @doctorinigo

🧠On Alzheimer’s as a metabolic disease 👇
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1) The more we learn about brain metabolism, the clearer it becomes: Alzheimer’s is not primarily a disease of amyloid plaques. It is a metabolic disease.
Let’s talk about what that means, and why the current paradigm must change:

2) The brain is the most glucose-demanding organ per unit volume. It’s a metabolic powerhouse of incredible efficiency…until it’s not.
When mitochondrial function declines, glucose metabolism falters and neuronal biogenetics fails, the stage is set for neurodegeneration.

3) The amyloid hypothesis, which has dominated Alzheimer’s research for decades, remains just that; a hypothesis which has failed to produce effective therapies. Meanwhile, the bioenergetic theory has robust scientific, mechanistic and clinical support.

4) Studies show that glucose uptake in the brain begins to decline decades before symptoms appear.
This precedes plaque accumulation. It is a warning sign that brain metabolism is breaking down.

5) What causes this decline?
Often, it is part of a larger systemic issue: insulin resistance, mitochondrial dysfunction, and metabolic inflexibility. In a vast number of people, AD is accompanied by previous glucose metabolism disorders like pre-diabetes or T2D.
Alzheimer’s is downstream of a broken metabolic system.

6) We must shift the focus from late-stage intervention to early detection and prevention targeting:
-Brain mitochondrial function
-Brain bioenergetics, specially glucose metabolism
-Lifestyle interventions: exercise, diet, metabolic therapy

7 If we keep treating Alzheimer’s as a protein-accumulation disorder, we will continue to fail.
If we treat it as a brain bioenergetic collapse, we open the door to prevention, to meaningful intervention, and possibly even reversal in early stages.

8) Because Alzheimer’s a systemic metabolic disease, not just a neurological one, we are likely to see Alzheimer’s manifesting at younger ages in metabolically unhealthy populations. Can we imagine a society where millions develop AD in their 40’s-50’s?…It would be the end of societies as we know them…

9) Bottom line:
Alzheimer’s is a metabolic disease of the brain. The paradigm must evolve: from neurocentric to metabolic, from symptomatic to preventative and from treatment to early intervention.

Unless we shift gears quickly,
we will keep missing the target, while the disease strikes younger populations and more often.
#Alzheimers #BrainMetabolism #Mitochondria