Why a PSEN1 carrier ended up obsessed with mitochondria

A genetic test result is what started this. Here's the reasoning that followed it, and why it ends at one specific mitochondrial protein.

The result

PSEN1 is one of the genes associated with early-onset familial Alzheimer's disease. Carrying it does something strange to your relationship with time, and it raises an obvious question: not just "what happens," but "why, mechanically, and where in that chain is there anything to grab onto?" That question is what turned into this project.

The thing worth questioning

The dominant story of Alzheimer's for decades has been about amyloid, the plaques. It's an important story. But a quieter one keeps getting overshadowed: the energy story. Neurons are ferociously demanding cells. They run on mitochondria. In Alzheimer's brains, mitochondrial dysfunction shows up early and often.

You can't run the most energy-hungry cells in the body on failing power plants and expect nothing to go wrong.

PSEN1 itself touches mitochondrial biology and calcium handling, not just amyloid processing. The neat wall between "the amyloid disease" and "the energy disease" turns out to be a lot more porous than the standard narrative suggests.

How the trail leads to VDAC1

Follow the energy thread and you keep arriving at the mitochondrial outer membrane, at its busiest doorway: VDAC1. It sits exactly where metabolism, calcium and cell-death decisions intersect. When mitochondria are stressed, VDAC1 is part of how they leak, how they trigger death, and how they set off inflammation by releasing mtDNA.

In a disease where neurons are stressed, leaking, dying and inflaming, VDAC1 is standing at the scene of the crime in each of those steps. What makes it more than an academic curiosity is that the mechanism is now druggable: see the VBIT compounds.

What this site is for

Not a hype machine, and not a substitute for talking to a doctor. A plain-spoken, evidence-graded map of what's known about mitochondrial health and VDAC1, built for anyone trying to make sense of the science, whether that's a fellow carrier, a patient, a researcher, or someone just curious how their cells actually work.