Neurology: A multicenter combined cohort confirms that plasma amyloid Aβ 42/40 reliably detects amyloid plaques in Alzheimer's disease

Amyloid plaques and neurofibrillary tangles are characteristic neuropathological changes in Alzheimer's disease (AD), accumulating in the brain for 10-20 years before most people develop symptoms of dementia
.

In cognitively normal individuals, biomarkers of AD pathology are used to identify persons at risk for AD dementia in order to participate in prevention trialsaimed at delaying or preventing the development of AD dementia symptoms

Amyloid plaques and neurofibrillary tangles are characteristic neuropathological changes in Alzheimer's disease (AD), accumulating in the brain for 10-20 years before most people develop symptoms of dementia

The recent rapid development of blood-based AD biomarkers promises to accelerate clinical trials and expand the availability of biomarker tests in the clinic

The accuracy of the IPMS plasma Aβ42/Aβ40 assay as a biomarker for brain amyloidosis needs to be validated in multiple cohorts to determine its accuracy and robustness

We used samples collected at multiple centers using different blood collection and processing protocols to determine the accuracy of plasma Aβ42/Aβ40 assays in classifying amyloid PET status in a global study

Plasma samples (n=465) were obtained from the United States (n=182, Alzheimer Disease Neuroimaging Initiative (ADNI, http://adni.
loni.
usc.
edu/) ) and Australia (n=183, the Australian Imaging, Biomarkers and Life>https://aibl.
csiro.
au/) ) and 3 large Alzheimer's disease (AD) study cohorts in Sweden (n=100, the Swedish BioFINDER study ( https://biofinder.
se/
)) .

Plasma Aβ42/Aβ40 was determined by high-precision immunoprecipitation mass spectrometry and compared with amyloid PET and cerebrospinal fluid Aβ42/Aβ40 reference

http://adni.

• There was good agreement between plasma Aβ42/Aβ40 and amyloid ε status (area under receiver operating characteristic curve, 0.
  84, 95% confidence interval, 0.
  80-0.
  87) in the combined cohort of 465 participants;
• Concordance improved after inclusion of APOE ε4 status (AuC 0.
  88, 95% CI 0.
  85-0.
  91)
  .
  
• The AUC value of cerebrospinal fluid amyloid Aβ42/Aβ4 0 was 0.
  85 (95%CI 0.
  78-0.
  91), and the AUC value of AOEε4 status was 0.
  93 (95%CI 0.
  89-0.
  97)
  .
  
• These findings were consistent across the 3 cohorts despite different protocols
  .
  
• Furthermore, this test performed similarly in cognitively normal and impaired individuals
  .
  

There was good agreement between plasma Aβ42/Aβ40 and amyloid ε status (area under receiver operating characteristic curve, 0.
84, 95% confidence interval, 0.
80-0.
87) in the combined cohort of 465 participants;

Concordance improved after inclusion of APOE ε4 status (AuC 0.
88, 95% CI 0.
85-0.
91)
.

The AUC value of cerebrospinal fluid amyloid Aβ42/Aβ4 0 was 0.
85 (95%CI 0.
78-0.
91), and the AUC value of AOEε4 status was 0.
93 (95%CI 0.
89-0.
97)
.

These findings were consistent across the 3 cohorts despite different protocols
.

Furthermore, this test performed similarly in cognitively normal and impaired individuals
.

     Plasma Aβ protein 42/Aβ protein 40 (Aβ42/Aβ40) is a reliable method for the detection of amyloid plaques, which can be used to aid in the diagnosis of AD, identify those at risk of developing dementia due to AD in the future, and improve participation in AD research and development.
Diversity of populations for clinical trials
.

Plasma Aβ protein 42/Aβ protein 40 (Aβ42/Aβ40) is a reliable method for the detection of amyloid plaques, which can be used to aid in the diagnosis of AD, identify those at risk of developing dementia due to AD in the future, and improve participation in AD research and development.
Diversity of populations for clinical trials
.

      This study provides a second type of evidence that plasma Aβ42/Aβ40, as measured by high-precision IPMS, can accurately diagnose brain amyloidosis in cognitively normal and impaired study participants

Source: Li Y, Schindler SE, Bollinger JG, et al.

Li Y, Schindler SE, Bollinger JG, et al.
Validation of Plasma Amyloid-β 42/40 for Detecting Alzheimer Disease Amyloid Plaques [published online ahead of print, 2021 Dec 14].
Neurology.
2021;10.
1212/WNL.
0000000000013211.
doi :10.
1212/WNL.
0000000000013211 Leave a message here