Dr. Yue Cai's latest paper was published on the  Neurology Journal . 

Plasma β-amyloid42 (Aβ42)/Aβ40 levels have shown promise in identifying Aβ-PET positive

individuals. This study explored the concordance and discordance of plasma Aβ42/Aβ40 positivity

(Plasma±) with CSF Aβ42/Aβ40 positivity (CSF±) and Aβ-PET positivity (PET±) in

older adults without dementia. Associations of Aβ deposition, cortical thickness, glucose metabolism,

and microglial activation were also investigated.

We selected participants without dementia who had concurrent plasma Aβ42/Aβ40 and Aβ-

PET scans from the Alzheimer’s Disease Neuroimaging Initiative cohort. Participants were

categorized into Plasma±/PET± based on thresholds of composite 18F-florbetapir (FBP)

standardized uptake value ratio (SUVR) ≥1.11 and plasma Aβ42/Aβ40 ≤0.1218. Aβ-PET–

negative individuals were further divided into Plasma±/CSF± (CSF Aβ42/Aβ40 ≤0.138), and

the concordance and discordance of Aβ42/Aβ40 in the plasma and CSF were investigated.

Baseline and slopes of regional FBP SUVR were compared among Plasma±/PET± groups,

and associations of regional FBP SUVR, FDG SUVR, cortical thickness, and CSF soluble

Triggering Receptor Expressed on Myeloid Cell 2 (sTREM2) levels were analyzed.

One hundred eighty participants (mean age 72.7 years, 51.4% female, 96 cognitively unimpaired, and

84 with mild cognitive impairment) were included.We found that the proportion of Plasma+/PET−

individuals was 6.14 times higher (odds ratio (OR) = 6.143, 95% confidence interval (CI)

2.740–16.185, p < 0.001) than that of Plasma-/PET+ individuals, and Plasma+/CSF− individuals

showed 8.5 times larger percentage (OR = 8.5, 95% CI: 3.031–32.974, p < 0.001) than Plasma-/

CSF+ individuals in Aβ-PET–negative individuals. Besides, Plasma+/PET- individuals exhibited

faster (p < 0.05) Aβ accumulation predominantly in bilateral banks of superior temporal sulcus

(BANKSSTS) and supramarginal, and superior parietal cortices compared with Plasma−/PET−

individuals, despite no difference in baseline FBP SUVRs. In Plasma+/PET+ individuals, higher CSF

sTREM2 levels correlated with slower BANKSSTS Aβ accumulation (standardized β (βstd) =

−0.418, 95% CI −0.681 to −0.154, p = 0.002). Conversely, thicker cortical thickness and higher

glucose metabolism in supramarginal and superior parietal cortices were associated with faster (p <

0.05) CSF sTREM2 increase in Plasma+/PET- individuals rather than in Plasma+/PET+ individuals.

These findings suggest that plasma Aβ42/Aβ40 abnormalities may predate CSF Aβ42/Aβ40 and

Aβ-PET abnormalities. Higher sTREM2-related microglial activation is linked to thicker cortical

thickness and higher metabolism in early amyloidosis stages but tends to mitigate Aβ

accumulation primarily at relatively advanced stages.