Advances Reported in Search for Blood Markers for Alzheimer’s Disease and Other Dementias
At the Alzheimer’s Association International Conference in Los Angeles, July 14-18, 2019, results from a study published in Nature were presented describing measures of blood amyloid isoforms associated with established Alzheimer’s disease (AD) markers.
Analysis of 201 samples from 70 individuals without cognitive impairment, 46 with mild cognitive impairment (MCI), 61 with AD, and 24 with nonAD dementia. Composite blood biomarker values significantly correlated with amyloid PET values (P < .001), MRI structural changes (P < .001), FDG-PET (P < .002), and Mini Mental State Examination (MMSE) (P <.001).
“We found that the plasma biomarker can detect earlier stages of amyloid deposition, even before dementia symptoms are apparent,” said Akinori Nakamura, MD, PhD, of the National Center for Geriatrics and Gerontology in Japan. “Our results suggest that the plasma biomarker may be useful in screening people who are at risk for Alzheimer’s.”
In another study, researchers evaluated whether concentrations of α-synuclein (a-syn) and its combinations with amyloid and tau (α-syn/Aβ and α-syn/tau) in red blood cells can accurately identify people with AD.
Levels of α-syn, α-syn/Aβ and α-syn/tau were analyzed in 39 people with early-stage AD and 39 age-matched people without AD. The individuals with AD received a biomarker-based diagnosis (CSF Aβ and CSF total-tau and/or phospho-tau or a positive brain amyloid PET scan).
“Our results showed that people with Alzheimer’s had much lower concentrations of α-synuclein and its combinations with amyloid and tau in their red blood cells, compared to healthy individuals,” said Filippo Baldacci, MD, of the Department of Clinical and Experimental Medicine, University of Pisa, Italy, and the Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital in Paris.
Another study focused on neurofilament light (NfL), also known as neurofilament light chain, as a biological marker for neurodegeneration in cerebrospinal fluid and plasma in a variety of neurologic disorders, including AD and other dementias.
An international study compared the levels of blood NfL across multiple neurodegenerative/neurological conditions. In the study, the original group (n=1,465) and a second independent cohort (n=852) included people with MCI, AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), Parkinson’s disease (PD), primary tauopathies, vascular dementia, Down syndrome (DS), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), clinical depression, and healthy elderly controls.
The researchers found that NfL was significantly increased in 8 neurodegenerative conditions including AD, FTD, DLB, corticobasal syndrome (CBS), ALS, and Down syndrome with dementia (DS-D), compared to healthy individuals.
“For the first time we have shown that NfL on its own is able to distinguish several neurodegenerative conditions when compared to healthy controls,” said Abdul Hye, PhD, of the Institute of Psychiatry, Psychology & Neuroscience, Kings College London. “These results hold promise for the use of NfL as a diagnostic tool and in clinical trials.”
“There is a great need for simple, reliable, inexpensive, non-invasive and easily available diagnostic tools for Alzheimer’s,” added Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association. "Families facing Alzheimer's now and in the future would benefit greatly from diagnostic tools that enable accurate diagnosis, earlier in the disease process, allowing for important care and planning. These new testing technologies, which are currently under development by industry and academic researchers, could also potentially be used to track the impact of therapies in clinical trials.”