Amazing stuff!
"A protein notorious for its role in Alzheimer’s disease may hold the key to supercharging the aging immune system, according to new research. Scientists have found that a byproduct of amyloid-beta rejuvenates T cells, boosting their tumor-fighting power and dramatically reducing cancer risk. ...
In the present study, five years of nationally representative surveys were analyzed, and the researchers found that adults over 59 with Alzheimer’s disease were a staggering 21 times less likely to develop cancer than those without the disease. ..."
"... Their new study ... reveals how a protein tied to Alzheimer’s disease also strengthens the immune system, offering insights that could inspire innovative treatments for cancer, aging and neurodegenerative diseases. ...
To test this finding, the researchers transplanted mitochondria from Alzheimer’s T-cells into aging T-cells that did not have Alzheimer’s. ...
“Older T-cells began functioning like young, active T-cells again. That was an incredible finding because it suggests a whole new way to think about rejuvenating the immune system.”
The results also revealed that amyloid beta contributes to cancer in another way – by depleting fumarate, a small molecule made inside mitochondria during energy production. Fumarate acts like a brake, keeping mitophagy from running out of control. When fumarate levels drop, cells recycle too many of their healthy mitochondria, resulting in a loss of strength. ..."
From the abstract:
"Patients with Alzheimer's disease (AD) have a decreased incidence of cancer, with a cross-sectional analysis of a nationwide sample of adults finding 21-fold higher odds of cancer diagnosis in non-AD individuals compared with those with AD.
In this study, we demonstrated that mitochondrial localization of AD-associated amyloid-β precursor protein (APP) and its cleavage product amyloid-β 40, but not mutant APP that lacks a mitochondrial localization signal, inhibits lipid stress–mediated hyperactive mitophagy in aging T cells, improving their antitumor functions.
Growth of melanoma xenograft or carcinogen-induced oral cancer models was highly reduced in AD mice. Additionally, adoptive cell transfer–based immunotherapy using aging T cells isolated from AD mice suppressed tumor growth.
The metabolic signature of stress-dependent mitophagy in T cells showed fumarate depletion, which was linked to decreased succination of Parkin and enhanced mitochondrial damage.
Mechanistically, APP interaction with the TOMM complex at the outer mitochondrial membrane attenuated trafficking of ceramide synthase CerS6 to mitochondria in aging AD T cells, preventing ceramide-dependent mitophagy. Thus, APP restored mitochondrial fumarate metabolism and Parkin succination, improving antitumor functions of AD T cells in vitro and in vivo.
Exogenous fumarate supplementation or healthy AD mitochondria transfer functionally mimicked the AD/APP phenotype in aging T cells, enhancing their antitumor activity to control tumor growth.
Moreover, T cells isolated from aging donors showed elevated mitophagy with fumarate depletion, which was restored in T cells isolated from age-matched patients with AD.
Together, these findings show that AD protects T cells against ceramide-dependent mitophagy and fumarate depletion to enhance antitumor functions."
Alzheimer's protein holds clues for fighting cancer (original news release)
Amyloid Beta Precursor Protein Prevents Aging Stress-Induced Mitophagy and Fumarate Depletion to Improve Anti-Tumor Functions of T Cells (possibly the preprint, open access with account, but appears to be dated)
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