Movement Disorder: Fudan Huashan Hospital, PET imaging reveals rare disease progression in frontotemporal dementia

Frontotemporal lobar degeneration (FTLD) is a spectrum of diseases that contains a high degree of heterogeneity in terms of clinical phenotype, neuropathological features, and genetic basis
.

FTLD with tauopathy (FTLD-tau) accounts for 40% of all FTLD cases, and pathogenic variants in the microtubule-associated protein tau (MAPT) gene are responsible for the inherited form of FTLD-tau

However, the relative abundance of 3R and 4R tau isoforms can be altered by pathogenic MAPT mutations, ultimately resulting in 3R, 4R or 3R+4R tauopathies
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Specifically, mutations in exon 10 and surrounding introns of MAPT, which together represent an important hotspot, lead to overproduction of 4R tau

Recent advances in tau positron emission tomography (PET) tracers have advanced our ability to identify tau deposits in the brain
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Although 18F-AV-1451 tau PET has been used to image patients with at least 10 different MAPT mutations, its diagnostic performance has been inconsistent

diagnosis

Another traditional tau tracer, 11C-PBB3, performed well in observing 4R tau aggregation in MAPT N279K variant patients, but it is clinically limited by its inherent metabolic instability and rapid clearance
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Although the utility of the second-generation tau radiotracer 18F-PI-2620 has been investigated in patients with progressive supranuclear palsy (PSP; a 4R tauopathy), its clinical value in MAPT mutation carriers remains unclear get an answer

Hereby, Xin-Yue Zhou et al.
from Fudan Huashan Hospital attempted to study the clinical utility of 18F-APN-1607 PET/CT in MAPT mutation carriers by analyzing 7 patient samples with different phenotypes
.

To this end, they thoroughly investigated the regional normalized uptake value ratio (SUVR) and patterns of tau deposition in a cross-sectional analysis

They included 7 MAPT mutation carriers (6 within exon 10 and 1 in exon 10) and 15 healthy controls
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All participants underwent 18F-APN-1607 PET/CT at baseline

Although the 7 subjects had different clinical phenotypes, all patients exhibited marked uptake of 18 F-APN-1607, which is characterized by high-contrast signal
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However, the anatomical localization of tau deposition is different in patients with different clinical symptoms

The significance of this study is the discovery that: 18 F-APN-1607 PET/CT imaging is important for detecting tau accumulation in MAPT mutation carriers
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Preliminary follow-up data also suggest the potential value of 18 F-APN-1607 PET/CT for monitoring the longitudinal trajectory of frontotemporal lobar degeneration caused by MAPT mutations
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18 F-APN-1607 PET/CT imaging is important for detecting tau accumulation in MAPT mutation carriers

 

Original source:
Zhou X, Lu J, Liu F, et al.
In Vivo 18 F‐APN‐1607 Tau Positron Emission Tomography Imaging in MAPT Mutations: Cross‐Sectional and Longitudinal Findings.
Mov Disord.
Published online November 29, 2021:mds .
28867.
doi:10.
1002/mds.
28867

Tau Positron Emission Tomography Imaging in MAPT Mutations: Cross‐Sectional and Longitudinal Findings.
Tau Positron Emission Tomography Imaging in MAPT Mutations: Cross‐Sectional and Longitudinal Findings.
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