Key biomarkers in familial Alzheimer’s disease
A Youngtimers Guide ・ Last Reviewed Nov 12 2025
A biomarker is something measurable in the body that signals what is happening biologically — in this case, inside the brain. Think of biomarkers like dashboard warning lights. They do not tell you exactly what is wrong or when the car will stop running, but they tell you something important is changing.
In this article, we’ll cover the key biomarkers most relevant to people at risk of familial Alzheimer’s diseased (FAD).
P-tau217
What it measures: A protein called tau is normally found in healthy brain cells. In Alzheimer's, tau becomes chemically altered in a way it should not be. P-tau217 measures one specific version of that abnormal change. It rises in direct response to the amyloid plaques that are a hallmark of Alzheimer's, making it one of the most Alzheimer's-specific blood markers available.
Why it matters for FAD: P-tau217 typically crosses into abnormal territory roughly 16 years before estimated symptom onset. It is also one of the best tools for estimating when symptoms are likely to begin. Research suggests it can help narrow that window to within about four years. That is remarkable precision for a blood test.
One important note: People in a clinical trial or taking an anti-amyloid or anti-tau medication will see p-tau217 levels fall as a result of treatment. That is a good sign clinically, but it means results need to be interpreted differently than for someone not on treatment.
NfL (neurofilament light chain)
What it measures: Neurons, the brain's nerve cells, have a kind of internal skeleton made of tiny filaments. When neurons are stressed, damaged, or dying, pieces of that skeleton break off and spill into the bloodstream. NfL measures those fragments. It is a signal of neuronal injury, the brain indicating that it is under real strain.
Why it matters for FAD: NfL is not specific to Alzheimer's. It can rise with many neurological conditions. Within FAD, it becomes meaningful in two important ways. First, it typically crosses into abnormal range about seven years before symptom onset. Second, the rate of change in NfL, how fast it is rising year over year, can distinguish mutation carriers from non-carriers as early as 16 years before symptoms. A single NfL number matters less than the trend over time.
NfL is also the cleanest marker to follow for someone on any kind of treatment, because anti-amyloid and anti-tau drugs do not directly suppress NfL the way they affect p-tau217. If neurodegeneration is actually slowing, NfL will reflect that honestly.
Normal NfL levels rise naturally with age. Here are approximate upper-normal reference ranges by age group.
[INSERT AGE TABLE]
GFAP (glial fibrillary acidic protein)
What it measures: The brain has cells called astrocytes, support cells that help keep neurons healthy and respond to injury. When amyloid plaques start forming, astrocytes become activated and release a protein called GFAP into the blood. It is a marker of brain inflammation and stress, the support system reacting to something going wrong.
Why it matters for FAD: GFAP can begin rising early in the disease process, sometimes before obvious neuronal injury shows up in NfL. However, it is not specific to Alzheimer's, and it rises significantly with age in healthy people. It is most useful when interpreted alongside other markers, not on its own.
One nuance specific to FAD: GFAP can behave differently depending on which mutation is present. Carriers of mutations on the APP gene may see different GFAP patterns than those with mutations on PSEN1 or PSEN2. The specific genetic mutation matters when interpreting this marker.
P-tau181
What it measures: Like p-tau217, this measures an abnormally altered version of the tau protein. It was developed earlier and is more widely available, but research has shown it is generally less precise than p-tau217 as an Alzheimer's-specific marker.
Why it matters for FAD: It remains useful, particularly when p-tau217 testing is not available. Think of it as a reliable earlier tool, meaningful but not the first choice when options exist.
Aβ42/40 ratio
What it measures: The brain naturally produces two versions of the amyloid protein: Aβ42 and Aβ40. In sporadic, non-inherited Alzheimer's, Aβ42 tends to get trapped in the brain as plaques form, so less of it circulates in the blood. Aβ40 stays relatively stable. The ratio of Aβ42 to Aβ40 in the blood therefore goes down, and a low ratio becomes a reliable proxy for amyloid buildup in the brain. Most commercial versions of this test are built around that pattern.
Why it matters for FAD: For FAD mutation carriers, it’s critical to understand that this test is designed for sporadic, non-inherited Alzheimer's, so its results can be seriously misleading when applied to FAD. Because mutations on PSEN1, PSEN2, and APP alter amyloid processing, FAD mutation carriers often have a chronically elevated Aβ42/40 ratio, regardless of how much amyloid is accumulating in the brain. For FAD mutation carriers, the ratio of Aβ42 to Aβ40 does not mean the same thing as it means in sporadic Alzheimer’s.