Abstract
Implementation of amyloid biomarkers in clinical practice would be accelerated if such biomarkers could be measured in blood. We analyzed plasma levels of Aβ42 and Aβ40 in a cohort of 719 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD) dementia and cognitively healthy elderly, using a ultrasensitive immunoassay (Simoa platform). There were weak positive correlations between plasma and cerebrospinal fluid (CSF) levels for both Aβ42 and Aβ40, and negative correlations between plasma Aβ42 and neocortical amyloid deposition (measured with PET). Plasma levels of Aβ42 and Aβ40 were reduced in AD dementia compared with all other diagnostic groups. However, during the preclinical or prodromal AD stages (i.e. in amyloid positive controls, SCD and MCI) plasma concentration of Aβ42 was just moderately decreased whereas Aβ40 levels were unchanged. Higher plasma (but not CSF) levels of Aβ were associated with white matter lesions, cerebral microbleeds, hypertension, diabetes and ischemic heart disease. In summary, plasma Aβ is overtly decreased during the dementia stage of AD indicating that prominent changes in Aβ metabolism occur later in the periphery compared to the brain. Further, increased levels of Aβ in plasma are associated with vascular disease.
Highlights
40/Aβ4 2 ratio and Aβligand retention on positron emission tomography (PET) was observed in APOE ε4 -negative subjects only[14]
We report that plasma Aβlevels correlate with cerebrospinal fluid (CSF) levels and with Aβplaque burden in the brain assessed using amyloid PET imaging
We show that plasma Aβ4 2 and Aβ4 0 are reduced in Alzheimer’s disease (AD) patients, especially during dementia stages, compared with cognitively healthy control individuals
Summary
40/Aβ4 2 ratio and Aβligand retention on PET was observed in APOE ε4 -negative subjects only[14]. The Australian Imaging Biomarkers and Lifestyle (AIBL) research team have reported that plasma levels of either Aβ4 0 or Aβ42 do not associate with AD or neocortical Aβburden[15]. The recently developed ultrasensitive Simoa technology offers improved analytical sensitivity[16] that makes it suitable for measurements of AD-related biomarkers in serum and plasma[17]. We measured plasma levels of Aβ42 and Aβ40 using Simoa assays in a cohort of 719 individuals including patients with subjective cognitive decline (SCD, n = 174), mild cognitive impairment (MCI, n = 214), AD (n = 57) and cognitively healthy elderly (n = 274). We combined plasma measurements with the analysis of CSF samples, amyloid PET, magnetic resonance imaging (MRI) and cognitive assessments in order to establish whether plasma Aβ42 and Aβ40 may be useful biomarkers of AD
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