Neurology: The relationship between amyloid and neuroinflammation is "ambiguous", and the lotus root is broken

Neuroinflammation, the activation of microglia and astrocytes, seems to play an important role in the pathogenesis of Alzheimer's disease (AD) and other diseases that cause dementia.
Metabolic risk factors, including obesity and insulin resistance, have been associated with cognitive decline and dementia.

However, little is known about the possible relationship between chronic low-grade inflammation, metabolic risk factors, neuroinflammation, and the neuropathology of AD.
Activated microglia overexpress 18-kDa translocator protein (TSPO), so PET imaging of a tracer bound to TSPO is used to assess neuroinflammation.

TREM2 is an innate immune receptor, which is selectively expressed by microglia in the central nervous system.
Its soluble variant (sTREM2) and YKL-40, a glycoprotein expressed by reactive astrocytes and microglia in the central nervous system, can be measured from CSF.
Studies have shown that these two types of neuroinflammation The markers of are increased in the early stages of AD.

Based on previous literature, it can be speculated that the increase in TSPO expression will be related to the accumulation of amyloid-β (Aβ) in the cerebral cortex, and that both TSPO expression and Aβ accumulation are related to neuroinflammation and CSF biomarkers of AD .
Previous studies have shown that middle-aged metabolic risk factors can predict brain Aβ accumulation and dementia.

Therefore, it is reasonable to assume that insulin resistance, obesity, and chronic low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) will be related to increased neuroinflammation.

In this way, Sini Toppala of the University of Turku in Finland performed brain PET imaging on 54 elderly volunteers without dementia, using TSPO radioligand [11C]PBR28 to quantify TSPO levels; using Aβ radioligand [11C] Pittsburgh compound B (PiB) can quantify Aβ levels.
Then explore the relationship between neuroinflammation and Aβ.

These 54 volunteers (average age 70.
0 years, 56% women, 51% APOE ɛ4 carriers) used the cerebellar cortex as the pseudo reference area and the reference area, and quantified TSPO and Aβ in 6 regions of interest.

At the same time, the values ​​of fasting venous blood glucose, insulin and high-sensitivity C-reactive protein (hs-CRP) were measured.

They found that there was no significant association between the TSPO and Aβ composite scores.

However, in amyloid-negative participants (PiB composite score ≤1.
5), higher PiB binding was associated with higher PBR28 binding, but in amyloid-positive participants, there was no such association.

Higher CSF soluble TREM2 (rs = 0.
72, p = 0.
01) and YKL-40 (rs = 0.
63, p = 0.
04) concentrations were associated with higher PBR28 composite scores.

Higher BMI, HOMA-IR, and hs-CRP are associated with higher PBR28 binding in the brain regions where Aβ accumulation was first detected in Alzheimer's disease.

The important significance of this study is that although there is no correlation between amyloid and neuroinflammation in the overall study group, in the subgroup of the early stages of amyloid pathology, neuroinflammation is associated with amyloid.

Original source:

neurology.
org/content/96/12/e1608" target="_blank" rel="noopener">Association of Early β-Amyloid Accumulation and Neuroinflammation Measured With \[11C\]PBR28 in Elderly Individuals Without Dementia
neurology.