Page 13 - AN-3-2

Advanced Neurology Limbic-predominant TDP-43 encephalopathy

and LATE-NC with HS exhibits a discreetly higher risk of of phosphorylated TDP-43 intracytoplasmic inclusions
apathy and inappropriate social behavior. However, these (NCIs) in vivo, although results are not yet available. 8
8
results have not been fully validated. Furthermore, there is
only one study suggesting that the diagnosis of LATE-NC 7.2. Biofluids biomarkers
may be associated with mild motor impairment, specifically At present, accessible biomarkers in biofluids for reliably
respiratory muscle weakness. Regarding the relationship determining abnormal TDP-43 inclusions in life are
53
between HS and LATE-NC, it has been suggested that it absent. To consider a possible pure LATE diagnosis during
40
does not lead to an increased risk of epileptic seizures. 35 life, a negative result in AT(N) biomarker studies should be
required in cases of amnestic predominant MCI. However,
7. Biomarkers recent years have seen promising advances in this field. In
At present, there are no specific diagnostic biomarkers DLFT, it has been demonstrated that phosphorylated TDP-
that allow for the accurate diagnosis of LATE during an 43 exocytosis is mediated by microvesicles (exosomes).
individual’s lifetime. However, there are some findings Studies have demonstrated promising results in detecting
in both structural magnetic resonance imaging and both TDP-43 and phosphorylated TDP-43 in exosomes
functional neuroimaging (PET) that may suggest the from CSF and plasma samples, especially applied to ALS
8
diagnosis of LATE in life. Efforts are also underway and DLFT, and, more recently, in LATE. Specifically,
52
to identify biochemical biomarkers to be measured in researchers have found that TDP-43 in exosomes from
accessible biofluids. plasma samples of individuals with LATE-NC, with or
without AD co-pathology, is significantly increased and
7.1. Neuroimaging findings would have good diagnostic capability. In addition, an
54
inverse relationship has been observed between plasma
Brain magnetic resonance imaging reveals hippocampal levels of TDP-43 (measured using SIMOA immunoassay
atrophy in the early stages, which is disproportionate to technology) and cortical thickness in the entorhinal cortex,
13
the pattern of atrophy in the rest of the brain, and with a as well as the volume of the parahippocampal and anterior
greater progression of hippocampal atrophy in longitudinal cingulate regions. This effect persists even after controlling
follow-up, related to the progression of amnestic for AT(N) biomarkers of AD pathology measured in
predominant cognitive decline. However, this atrophy is plasma. 55
52
not limited to the hippocampal region but is also described
in the inferior frontal region, anterior temporal lobe, and On the other hand, studies with a more holistic
insular cortex (corresponding to the anatomopathological approach aimed at identifying a proteomic signature
progression of the stages LATE-NC). This pattern becomes specific to LATE-NC in CSF have not yielded particularly
3
more evident as cognitive decline progresses and begins to promising results. They have only observed differences in
affect other cognitive domains, even if it continues to be the expression of four proteins between non-LATE-NC and
predominantly amnestic in nature during the follow-up. LATE-NC individuals: RBP4, MIF, IGHG3, and ITM2B.
These changes are more evident if LATE-NC coexists with Among these, only RBP-4 (retinol-binding protein 4) has
AD pathology. When HS is present, it usually presents been confirmed through western blot to have different
30
asymmetrically. 3 levels between the two groups, requiring further validation
in future studies. 56
Brain FDG-PET imaging reveals hypometabolism with
a clear predominance in regions involved in the limbic 8. Treatment
system, with relative preservation of regions involved in
neocortical functions. From the early stages, there is a At present, there is no scientific evidence supporting
disproportionate hypometabolism in the inferior medial the use of available symptomatic treatments for AD in
temporal region, which is more pronounced compared to cases of possible LATE. It remains unknown whether the
pure AD. 52 symptomatic benefit of acetylcholinesterase inhibitors and/
or memantine offers the same, lower, or higher benefit in
A typical clinical syndrome (amnestic predominant the presence of AD and LATE-NC copathology. There
3
MCI with negative AT[N] biomarkers in the elderly is uncertainty about whether the effect of anti-amyloid
population) along with a pattern of hippocampal- treatments proposed and authorized by the Food and
predominant atrophy and the presence of hypometabolism Drug Administration of the US for use in AD, such as
in the medial temporal lobe may have a high diagnostic lecanemab, varies depending on the presence or absence
57
value for LATE in clinical practice. To enhance the of LATE-NC copathology. To advance our understanding
8
diagnostic performance of LATE, progress is being made of the implications of AD copathology with LATE-NC,
in the development of radiotracers that allow the detection optimizing diagnostic biomarkers for the in-life detection

Volume 3 Issue 2 (2024) 7 doi: 10.36922/an.2603