Why a PSEN1 carrier ended up obsessed with mitochondria

Every blog like this has an origin story. Mine starts with a genetic test result and a decision about what to do with it.

The result

I'm a PSEN1 carrier. PSEN1 is one of the genes associated with early-onset familial Alzheimer's disease. Learning that about yourself does something strange to your relationship with time — and, if you're wired the way I am, it makes you want to understand. Not just "what happens," but "why, mechanically, and where in that chain is there anything to grab onto?"

I could have looked away. I chose to read instead. Reading turned into a project, and the project turned into this blog.

The thing that kept bugging me

The dominant story of Alzheimer's for decades has been about amyloid — the plaques. Important story. But the more I read, the more I kept tripping over a quieter one: the energy story. Neurons are ferociously demanding cells. They run on mitochondria. And 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 turns out to touch mitochondrial biology and calcium handling, not just amyloid. The neat wall between "the amyloid disease" and "the energy disease" started to look a lot more porous the deeper I went.

How I landed on VDAC1

Once you're following the energy thread, you keep arriving at the mitochondrial outer membrane — and 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.

For someone worried about a disease where neurons are stressed, leaking, dying and inflaming — VDAC1 is standing right at the scene of the crime in each of those. I didn't set out to care about a specific pore. I followed the mechanism and it kept pointing here. Then came the hook that made it more than academic: the VBIT compounds.

What I want this blog to be

Not a journal. Not a hype machine. Just an honest, curious, plain-spoken notebook from someone with a personal reason to get this right and no incentive to oversell it. If you're a fellow carrier or patient, I hope this makes the science feel less like a locked room. If you're a researcher, I hope you'll correct me when I'm wrong. If you're just curious — welcome.