Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer's disease.

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer's disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression.

Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update.

Neuroinflammation is a significant contributor to Alzheimer's disease (AD). Until now, PET imaging of the translocator protein (TSPO) has been widely used to depict the neuroimmune endophenotype of AD. The aim of this review was to provide an update to the results from 2018 and to advance the characterization of the biological basis of TSPO imaging in AD by re-examining TSPO function and expression and the methodological aspects of interest. Although the biological basis of the TSPO PET signal is obviously related to microglia and astrocytes in AD, the observed process remains uncertain and might not be directly related to neuroinflammation. Further studies are required to re-examine the cellular significance underlying a variation in the PET signal in AD.

Taking the A Train? Limited Consistency of Aß42 and the Aß42/40 Ratio in the AT(N) Classification.

The consistency of cerebrospinal fluid amyloid-ß (Aß)42/40 ratio and Aß42 has not been assessed in the AT(N) classification system. We analyzed the classification changes of the dichotomized amyloid status (A+/A-) in 363 patients tested for Alzheimer's disease biomarkers after Aß42 was superseded by the Aß42/40 ratio. The consistency of Aß42 and the Aß42/40 ratio was very low. Notably, the proportions of "false" A+T-patients were considerable (74-91%) and corresponded mostly to patients not clinically diagnosed with Alzheimer's disease. Our results suggest that the interchangeability of Aß42/40 ratio and Aß42 is limited for classifying patients in clinical setting using the AT(N) scheme.