SherlockMS and the Case of the Late Witness

I stared at a blank sheet of paper and thought about my brother’s criminal cases. Ordinary criminal cases, of course: stolen jewels, vanished heirs, lords with alibis polished like saddle leather. And then something far more elegant wandered into my mind: neuroscience. A case that didn’t smell of gunpowder, but of time. ⏳
And of a tiny, unremarkable thread buried deep inside nerve cells. “How tedious,” I muttered. “A witness who shows up months too late.”

Chapter 1: The Witness Is Named NfL

They had asked for my counsel again, because a signal had appeared in blood and cerebrospinal fluid; one everyone wanted to treat like an alarm bell: neurofilament light, or NfL. Think of NfL as the steel framework of a high-rise: not pretty, but essential. When something goes wrong anywhere in the nervous system, fragments become measurable. And people cheer: “Ah! A biomarker! It tells us everything!”
How naïve. Because I’ve learned this: a biomarker can be honest and still mislead you if you catch it at the wrong time.

Chapter 2: The Trick of the Label

This time the method was almost poetic. They gave the system a marker- nothing dangerous, nothing dramatic - a stable isotope–labelled building block that the body incorporates into proteins. Invisible ink for molecules.
The idea was simple: when new NfL is produced, it will eventually carry the label. Then you can track when the fresh goods appear. A dream for any detective who loves order.
And then something happened that even I found amusing: In tissue, the label appeared quickly.
But in cerebrospinal fluid… it took its time. A great deal of time.
Not hours. Not days. Months. I took a sip of tea and smiled; the way only someone smiles who has just watched a lovely theory collapse.

Chapter 3: A Witness Who Arrives Late

Most people expected the following: if neurons lose NfL, surely “new” NfL should show up rapidly somewhere measurable, yes? Wrong.
What becomes measurable quickly is often not freshly produced at all. It is, rather, what my brother would call in his cases the dust of the past: old stock suddenly released when something tears.
Because freshly labelled NfL—this is the point I enjoy explaining with a gentle, condescending tone—has a surprisingly long journey before it becomes visible in cerebrospinal fluid as a “new trace.”
This isn’t a small detail. It’s the whole case.

Chapter 4: Three Suspects, One Victim and Me as Judge

So what does it mean when NfL in blood or CSF suddenly rises?
Allow me to introduce the usual suspects; and yes, I see you paying attention now:

1. The leak 🚧 Axons break, and existing NfL pools “spill out.” Fast, messy: classic accident or violence.
2. The courier service 📦 NfL may be transported outward in a regulated way: less accident, more planned delivery. That would create delays.
3. The clogged drain 🚰

If clearance from the brain is impaired, NfL lingers: like a crime scene nobody cleans up. Then came the second file: a parallel case from cell culture, neurons from iPSC models. And again: not an immediate trail, but a timing trick.
Labelled NfL appeared in the surrounding medium with a delay of 3–6 days.
And now comes the part where I usually leave the room, because everyone starts nodding too eagerly:
An early NfL rise can mean many things, but it does not automatically mean that massive amounts of new NfL have just been produced.

That is the brain’s real criminal artistry:

• In tissue, NfL is built quickly and then remains stably incorporated (detectable long after labelling).
• In the CSF world, “new” NfL emerges sluggishly, with very slow dynamics.

“The culprit,” I say dryly, “is not always the disease. Sometimes it’s the interpretation. And its accomplice is the time window.”
Because the witness - newly labelled NfL - arrives much later. And anyone who questions the wrong witness at the wrong time doesn’t solve a case; they merely write a bad report.

Chapter 5: Why the Brain Amuses Me Every Time

Do you know what fascinates me most?
The brain is not merely an organ. It is a crime scene with its own logistics: barriers, transport routes, delays, storage, detours. It is like London itself; everything is connected, and yet nothing arrives on time.
And that is exactly why I love cases like this: not because they are loud, but because they are cleverer than the people measuring them. I set down my pen, looked out the window, and said only to myself: “The truth is rarely hidden. It is usually just… late.”
Your SherlockMS