Inside the mind of a 19-year-old with Alzheimer’s

Can a 19-year-old have Alzheimer’s disease?

That’s what neurologists in China think. In 2023, they reported a case of a 19-year-old male who had experienced gradual memory decline since he was 17.^[] They have diagnosed him with probable Alzheimer’s disease.

“Based on imaging and biomarkers of the CSF [cerebrospinal fluid], it was a probable Alzheimer's diagnosis. However, what is interesting, I thought, with this case, is that the patient [himself] is not carrying any of the usual gene mutations that are usually associated with early onset Alzheimer's disease, especially in [people] under 30 years old. Usually, there's a gene mutation that's associated and found,” Jasmin Dao, MD, PhD, a pediatric and adult neurologist at Miller Children's & Women's Hospital Long Beach and MemorialCare Long Beach Medical Center in California, who was not involved in the case study, tells MDLinx.

Memory decline at age 17

The cerebrospinal fluid of the teenager also had an increased concentration of p-tau181 and a decreased amyloid-β 42/40 ratio.

Despite this, no known gene mutations were found.

No gene mutations detected

“That age is really surprising, but not totally out of the realm of possibilities for familial Alzheimer's disease, which is generally very rare. So when people hear about Alzheimer's disease … usually they're thinking about sporadic Alzheimer's disease, which usually happens in the 70s, 60s, potentially 80s, but most likely around the 70s or so. This familial Alzheimer's disease is a very rare form of genetic Alzheimer's disease, where every single generation in the family will have the disease,” Kyan Younes, MD, a clinical assistant professor of neurology and neurological sciences at Stanford University School of Medicine, tells MDLinx.

“There are basically three genetic mutations that cause familial Alzheimer disease: presenilin-1 (PS-1), presenilin-2 (PS-2), and APP. This is basically a different form of Alzheimer disease than what is typically thought of.”

Both experts say that early onset Alzheimer’s at the age of 19 is rare.

But Dr. Dao notes that if young patients present with symptoms that could be due to Alzheimer’s, a diagnosis may be delayed due to the rarity of the disease within that age group.

Other possibilities

PET scans showed no abnormal tau protein in the brain and no obvious amyloid plaques in the 19-year-old. Dr. Younes says that this is an important factor in considering the case objectively.

“This discrepancy with the CSF finding cannot be ignored. If this is florid sporadic Alzheimer’s disease, we should’ve expected positivity in one or both of these PET images. The PET images are more believable than the cerebrospinal fluid as they are used as the gold standard for which CSF and blood AD markers are compared against. The CSF normal ranges they report are most likely based on a population much older than the patient. I don’t know if there is data for normal CSF tau and amyloid ranges at this young age,” he says.

He argues that, at such a young age, other conditions like frontotemporal dementia should also be considered, as well as more genetic testing.

“Although this is a very sad story, with regards to AD [Alzheimer’s disease] diagnosis, [the neurologists’]concern for AD is appropriate but remains to be confirmed. Negative amyloid and tau PET scans are red flags pointing toward something else other than AD. Negative PET can be seen in some genetic forms of Alzheimer’s disease. They tested the common ones, but considering more genetic testing, such as long-read sequencing, could shed light on [or] discover other genetic mutations this patient might have. Ultimately, the confirmation of the diagnosis with 100% certainty requires pathological examination of the brain,” he says.