PHILADELPHIA, PA.- Alzheimers disease and related diseases can still only be confirmed in deceased patients brains via autopsy. Even so, the development of biomarkers can give patients and their families answers during life: Alzheimers disease can be accurately detected via peptides and proteins in a patients cerebrospinal fluids (CSF), which can be collected through a lumbar puncture and tested while the patient is alive. In 2018, a new framework suggested combining three Alzheimers disease biomarkers in CSF pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N), collectively called ATN. According to recent research from the
Perelman School of Medicine at the University of Pennsylvania, the ATN framework can be extended to detect another neurodegenerative condition: frontotemporal degeneration.
Patients with frontotemporal degeneration can experience a range of symptoms, including behavioral changes, executive dysfunction, and language impairments. Distinguishing frontotemporal degeneration from Alzheimers disease can be a challenge for clinicians: the symptoms of frontotemporal degeneration can sometimes overlap with Alzheimers disease, and a subset of patients can even have both pathologies. Biomarkers can fill the gap by providing evidence of whether Alzheimers pathology underlies a patients symptoms.
CSF biomarkers work similarly to a pregnancy test, offering a simple positive or negative result when enough of a substance is detected. But like a pregnancy test, biomarkers for Alzheimers disease can provide false negatives or positives, said lead investigator Katheryn A.Q. Cousins, PhD, a research associate in the Frontotemporal Degeneration Center in the Department of Neurology at Penn Medicine. Alzheimers is a diverse disease, and it is common for other conditions to also be present in the brain. The ATN framework may provide a more complete look at a persons diagnosis and give us a much richer understanding of not only Alzheimers disease, but other co-occurring neurodegenerative conditions. However, to accomplish this, additional biomarkers that can detect other neurodegenerative conditions are critically needed.
The findings, published in Alzheimers and Dementia: The Journal of the Alzheimers Association, show that ATN incorporating neurofilament light chain (NfL) may provide a more accurate and precise diagnosis for patients with frontotemporal degeneration. NfL is a protein abundant in the brain, whose levels increase as degeneration progresses. Cousins work shows that CSF NfL may be a more accurate marker of neurodegeneration for patients with frontotemporal degeneration, including for Alzheimers disease.
While the ATN framework is very exciting and offers much opportunity for patients with Alzheimers disease, these biomarkers dont capture every case of the disease. We want to be able to detect and treat every patient with neurodegenerative disease as early as possible, and more research is needed to fully understand how biofluids track with the disease process, said Cousins. I am eager to conduct additional research into which patients might be missed by these markers, what they have in common, and what causes the pathological and clinical differences in the disease.
This study was funded by the Swedish Research Council (2018-02532); the European Research Council, (681712); Swedish State Support for Clinical Research (ALFGBG-720931); the Alzheimer Drug Discovery Foundation (201809-2016862); the Swedish Alzheimer Foundation, (AF-742881); European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236); and the Alzheimers Association Research Fellowship (AARF-16-44368).