TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Langerscheidt, Felix
A1  - Wied, Tamara
A1  - Al Kabbani, Mohamed Aghyad
A1  - Eimeren, Thilo van
A1  - Wunderlich, Gilbert
A1  - Zempel, Hans
T1  - Genetic forms of tauopathies: inherited causes and implications of Alzheimer's disease-like TAU pathology in primary and secondary tauopathies
JF  - Journal of Neurology
N2  - Tauopathies are a heterogeneous group of neurologic diseases characterized by pathological axodendritic distribution, ectopic expression, and/or phosphorylation and aggregation of the microtubule-associated protein TAU, encoded by the gene MAPT. Neuronal dysfunction, dementia, and neurodegeneration are common features of these often detrimental diseases. A neurodegenerative disease is considered a primary tauopathy when MAPT mutations/haplotypes are its primary cause and/or TAU is the main pathological feature. In case TAU pathology is observed but superimposed by another pathological hallmark, the condition is classified as a secondary tauopathy. In some tauopathies (e.g. MAPT-associated frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease (AD)) TAU is recognized as a significant pathogenic driver of the disease. In many secondary tauopathies, including Parkinson's disease (PD) and Huntington's disease (HD), TAU is suggested to contribute to the development of dementia, but in others (e.g. Niemann-Pick disease (NPC)) TAU may only be a bystander. The genetic and pathological mechanisms underlying TAU pathology are often not fully understood. In this review, the genetic predispositions and variants associated with both primary and secondary tauopathies are examined in detail, assessing evidence for the role of TAU in these conditions. We highlight less common genetic forms of tauopathies to increase awareness for these disorders and the involvement of TAU in their pathology. This approach not only contributes to a deeper understanding of these conditions but may also lay the groundwork for potential TAU-based therapeutic interventions for various tauopathies.
KW  - Primary tauopathy
KW  - Tauopathies/genetics/pathology
KW  - Alzheimer’s disease
KW  - Alzheimer Disease/genetics/pathology
KW  - Humans
KW  - TAU
KW  - MAPT
KW  - tau Proteins/genetics/metabolism
KW  - Secondary tauopathy
KW  - Genetic tauopathy
Y1  - 2024
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-83744
SN  - 0340-5354
SS  - 0340-5354
U6  - https://doi.org/10.1007/s00415-024-12314-3
DO  - https://doi.org/10.1007/s00415-024-12314-3
PM  - 38554150
VL  - 271
IS  - 6
SP  - 2992
EP  - 3018
S1  - 27
PB  - Springer
ER  -