[ExI] The tedium

[Stuart LaForge]

On 2026-01-12 02:21, Rafal Smigrodzki via extropy-chat wrote:
> I briefly perused recent posts to ExI and I must admit to a certain
> sense of tedium... so much talk about the one whom I will not name,
> and about the wonders of socialism, so few discussions of...
> interesting stuff.
> 
> Have you heard that 75% of all so-called sporadic Alzheimer's disease
> is actually caused by mutations in just one gene (and it's not
> amyloid)? It's ApoE. That's an amazing development, really puts into
> perspective how misguided most AD research was in the past 50 years.--

I actually recall learning that one mutant allele of ApoE was linked to 
Alzheimer's disease and another mutant allele was linked to heart 
disease all the way back in the late 1990s in my Human Genetics classes 
at university. Maybe they just didn't have the tools to follow up on 
that knowledge until recently.

On a related topic, did you hear that a drug candidate called P7C3-A20 
can reverse Alzheimer's disease in mouse models? It seems to work by 
restoring NAD+ homeostasis in affected cells causing them to clear 
amyloid by normalizing gene activation.

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00608-1

Abstract

Alzheimer’s disease (AD) is traditionally considered irreversible. Here, 
however, we provide proof of principle for therapeutic reversibility of 
advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment 
with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) 
homeostasis, reverses tau phosphorylation, blood-brain barrier 
deterioration, oxidative stress, DNA damage, and neuroinflammation and 
enhances hippocampal neurogenesis and synaptic plasticity, resulting in 
full cognitive recovery and reduction of plasma levels of the clinical 
AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in 
tau-driven PS19 mice and protects human brain microvascular endothelial 
cells from oxidative stress. In humans and mice, pathology severity 
correlates with disruption of brain NAD+ homeostasis, and the brains of 
nondemented people with Alzheimer’s neuropathology exhibit gene 
expression patterns suggestive of preserved NAD+ homeostasis. Forty-six 
proteins aberrantly expressed in advanced 5xFAD mouse brain and 
normalized by P7C3-A20 show similar alterations in human AD brain, 
revealing targets with potential for optimizing translation to patient 
care.
-------------

This is hopeful news.

Stuart LaForge