Alzheimer Dementia: What are the characteristics of amyloid distribution in different areas of the brain?

Positron emission tomography (PET) Tau imaging is an important biomarker of neuropathological changes in Alzheimer's disease (AD) and the end point of clinical trials
.
A direct interpretation of the Tau PET results may be that the intake of tracer increases linearly with the development of the disease

However, existing research provides an incomplete picture of the tau PET signal over time
.
Several studies have attributed the slowing or reduction of regional tracer retention to measurement errors or processing artifacts

First, in the late stage of the disease, the pathological burden of tau may stabilize or decrease due to limiting factors such as the ability of the tissue to retain pathological aggregates
.

In addition, biological changes may affect the binding of the tracer to tau aggregates
.
In fact, the combination of 18F-flortaucipir with immature tau, mature tau, and different tau species isolated from cerebrospinal fluid (CSF) is different

Atypical AD includes non-amnesia and early-onset amnesia variants, which provides a unique background for studying the longitudinal changes of tau PET imaging
.
As atypical AD patients have greater neocortical tau burden and less hippocampal tau in histopathological examinations, tau PET quantification may be less interfered by artifacts related to regional segmentation or choroid plexus off-target binding.

Magnetic resonance imaging (MRI) and PET studies have always shown that patients with atypical and typical amnesia have different disease spread patterns, logarithmic variant primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), and cortical matrix synthesis Signs (CBS), behavioral/performing AD (bvAD; note the mixed result of bvAD atrophy), and early-onset amnesia (aAD) have obvious neocortical lesions
.
Few longitudinal studies have investigated atypical or non-amnestic syndromes in a way that clearly correlates radioligand uptake with patient phenotype

Compared with typical cases of late-onset amnesia, these features facilitate the imaging of tau accumulation in a larger brain volume and a larger time window.
In these cases, neocortical disease is limited to Braak stage IV-VI
.

In this way, Jeffrey S.
Phillips and others at the University of Pennsylvania explored the significant slowing or reduction of longitudinal 18F-flortaucipir signals in atypical AD patients at the Frontotemporal Degeneration Center (FTDC) of the University of Pennsylvania
.

The goal is to determine whether this change is more likely to be due to measurement errors, including processing artifacts and random statistical noise, or is consistent with expected biological changes in atypical AD
.

Core hypothesis: Early disease areas will show high baseline 18F-flortaucipir signal, but longitudinally slow or reduce tracer binding, while advanced disease areas will show lower baseline tau and larger subsequent increases

In addition, it is also predicted that the changes in tau signal will vary with the severity of the disease and age.
Compared with the milder cases, the later cases show a reduction in longitudinal changes
.
Finally, we also assessed the prevalence of these analyses for typical AD by analyzing longitudinal 18F-flortaucipir data in a larger sample of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants

They evaluated 24 amyloid beta (Aβ)+ patients with atypical, early-onset absence or non-absence AD ​​and 62 Aβ- and 132 Aβ+ Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants in 18 F-flortaucipir PET imaging changes between regions and individuals
.

In atypical AD, the uptake of 18-F-flortaucipir slows or decreases over time in areas with higher baseline signals and in older, more impaired individuals
.

Compared with the late region, ADNI participants had less longitudinal changes in the early Braak stage region
.

The uptake of radioligand (radioligand uptake) will stabilize in late neurodegeneration and then decline
.

Further research should investigate whether these results are applicable to other radioligands and whether they are related to changes in the radioligand binding site structure or accessibility

Original source:
Phillips JS, Nitchie FJ, Da Re F, et al.
Rates of longitudinal change in 18 F‐flortaucipir PET vary by brain region, cognitive impairment, and age in atypical Alzheimer's disease.
Alzheimer's & Dementia .
Published online September 13, 2021:alz.
12456.
doi:10.
1002/alz.
12456