By Lucy Piper, medwireNews reporter
medwireNews: Midlife measurement of blood-based biomarkers is not significantly associated with late-life amyloid positivity, suggests research from the ARIC study.
However, there is a positive association with the change in biomarkers between midlife to late-life and positron emission tomography (PET) amyloid positivity, said Priya Palta (New York University, USA).
She presented the findings at the Alzheimer’s Association International Conference 2024 in Philadelphia, Pennsylvania, USA.
“Early detection of Alzheimer’s disease pathology and neurodegeneration may be critical to dementia prevention,” Palta commented. She noted that blood-based biomarkers may make early detection easier in community-dwelling populations because they are “less burdensome, more cost-effective, and easier to implement in diverse populations” than using cerebrospinal fluid or performing PET scans.
She used logistic regression models to assess whether plasma biomarkers measured in midlife, at a mean age of 58.5 years, or later life, at a mean age of 76.2 years could predict late-life PET amyloid positivity, defined as a global cortex standardized uptake value ratio of greater than 1.2.
The biomarkers of interest were the amyloid-β 42 to amyloid-β 40 ratio, phosphorylated (p)-tau181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).
Data for a subset of 261 Atherosclerosis Risk in Communities (ARIC) participants were assessed, of whom 60% were White and 40% were Black. Most of the patients had no cognitive impairment (73.6%) and no apolipoprotein (apo)E ɛ4 alleles (66.5%).
None of the plasma biomarkers measured in midlife were significantly associated with PET amyloid positivity measured a median of 19.3 years later (interquartile range [IQR] 18.7 to 19.9 years), Palta told delegates.
By comparison, measurement of the plasma biomarkers amyloid-β 40/42 ratio, p-tau181, and GFAP, but not NfL, in later life – a median of 1.6 years (IQR 1.1–2.9 years) before PET – were significantly associated with PET amyloid positivity, after taking into account a number of covariates known to affect blood-based biomarkers.
These were age, sex, race, education, apoE ɛ4 status, time between blood draw and PET, estimated glomerular filtration rate, body mass index, smoking status, physical activity, and comorbidities including diabetes, hypertension, coronary heart disease, total cholesterol, and high-density lipoprotein cholesterol.
The odds ratios for amyloid positivity were a significant 2.12 for the amyloid-β 40/42 ratio, 1.76 for p-tau181, and 1.72 for GFAP.
Palta also noted significant odds ratios for the change in the biomarkers between midlife and later life, at a respective 1.38, 1.89, and 1.62.
She said that the greatest classification accuracy for this community-dwelling population was achieved by using late-life biomarker assays together with demographic information, at an area under the receiver operating characteristic curve (AUC) of 77% and 82%, respectively. Adding apoE ɛ4 status to these two measures did not improve on the AUC of 82%, Palta pointed out.
She added that the “classification accuracy in this community-dwelling population was lower or comparable to prior studies.”
Palta concluded that “additional longitudinal research is needed to determine how early in the life course blood-based measures can detect signs of dementia-related pathology.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
AAIC24; Philadelphia, Pennsylvania, USA: July 28–Aug 1
