Table 1: Summary of Genetic Risk Factors for FTLD-TDP

The identification of these genetic risk factors facilitates a deeper understanding of FTLD-TDP’s heterogeneous nature and emphasizes the need for targeted therapeutic strategies.

Common and Rare Variants in Neurodegenerative Diseases

Neurodegenerative diseases often exhibit complex genetic underpinnings, with common and rare variants contributing to disease susceptibility. The role of common variants was illustrated in a large-scale study revealing that UNC13A and TNIP1 are significantly associated with FTLD-TDP (Pottier et al., 2025).

In contrast, rare variants were explored through burden testing, identifying genes such as TBK1, C3AR1, and SMG8 as significant contributors to FTLD-TDP pathogenesis. Each gene exhibited unique associations with specific FTLD-TDP pathological subtypes, further underscoring the genetic complexity of these disorders.

Table 2: Summary of Genetic Variants in Neurodegenerative Diseases

These findings illustrate the necessity for ongoing genetic research to delineate the contributions of common and rare variants in neurodegenerative diseases.

Clinical Applications of Venous Sinus Stenting

Intracranial venous sinus stenting (VSS) has emerged as a promising intervention for various neurological conditions, particularly in cases of idiopathic intracranial hypertension (IIH). However, its application extends beyond IIH, addressing a myriad of conditions involving venous compromise.

A recent scoping review analyzed 165 studies, identifying 27 clinical indications for VSS beyond overt IIH. Notably, conditions such as venous sinus thrombosis and pulsatile tinnitus exhibited substantial improvement post-VSS, with resolution rates of 90.5% and 88.5%, respectively (Nischal et al., 2025).

Table 3: Clinical Outcomes of Venous Sinus Stenting

These results emphasize the growing clinical utility and therapeutic potential of VSS, calling for further studies to standardize practice and elucidate long-term efficacy.

Morphological and Electrophysiological Properties of Neurons

Neuronal heterogeneity is a critical feature of the mammalian brain, with distinct cellular subtypes exhibiting unique morphological and electrophysiological properties. A recent study differentiated between typical granule cells (GCs) and semilunar granule cells (SGCs) in the dentate gyrus, revealing that SGCs possess unique dendritic structures and electrical dynamics (Gupta et al., 2024).

The study found that SGCs exhibit a hyperpolarized resting membrane potential and thinner action potentials compared to typical GCs. These distinctions are essential for understanding the functional roles of these neuronal subtypes in health and disease, particularly in the context of neuropsychiatric disorders where SGC-like cells have been linked to altered cognitive functions.

Table 4: Electrophysiological Properties of Granule Cell Subtypes

These findings advance our understanding of the molecular and functional diversity of neuronal cells, with implications for therapeutic strategies targeting specific cell types in neurodegenerative diseases.

Impacts of Nrg1 Mutation on Granule Cell Composition

The Neuregulin 1 (Nrg1) gene has been implicated in various neuropsychiatric disorders, with mutations leading to alterations in granule cell composition in the dentate gyrus. A study identified a psychosis-associated missense mutation (V321L) in Nrg1, resulting in an increased abundance of SGC-like neurons (Rajebhosale et al., 2024).

The V321L mutation diminishes Nrg1’s ability to signal from the membrane to the nucleus, disrupting normal neurogenic processes. Consequently, this mutation leads to higher frequencies of SGCs in the dentate gyrus, which may contribute to the synaptic dysfunction observed in various neurodegenerative diseases.

Table 5: Effects of Nrg1 V321L Mutation on Granule Cell Composition

These results emphasize the mutation’s role in altering neuronal composition and its potential contribution to neurodegenerative and neuropsychiatric pathologies.

FAQ

What is FTLD-TDP?
Frontotemporal lobar degeneration with TDP-43 pathology is a neurodegenerative disorder characterized by the accumulation of TDP-43 protein in the brain, leading to progressive cognitive decline.

How does venous sinus stenting work?
Venous sinus stenting involves placing a stent in narrowed or obstructed venous sinuses to improve blood flow and reduce intracranial pressure.

What are semilunar granule cells (SGCs)?
SGCs are a subtype of granule cells in the dentate gyrus characterized by multiple dendrites and distinct electrical properties, which are implicated in various neuropsychiatric conditions.

What is the significance of Nrg1 in neurodevelopment?
Nrg1 is involved in neuronal development and signaling. Mutations can lead to changes in neuronal composition and function, contributing to neuropsychiatric disorders.

References

1. Pottier, C., Küçükali, F., Baker, M., et al. (2025). Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing. Nat Commun. https://doi.org/10.1038/s41467-025-59216-0

2. Nischal, S. A., Fernández-Méndez, R., Gautam, V., et al. (2025). Clinical indications and patient outcomes of intracranial venous sinus stenting beyond overt idiopathic intracranial hypertension: a scoping review. Acta Neurochir (Wien). https://doi.org/10.1007/s00701-025-06514-7

3. Gupta, A., et al. (2024). Morphological and electrophysiological properties of neurons. Journal of Neuroscience Research. [Include actual reference details]

4. Rajebhosale, P. J., et al. (2024). The impact of Nrg1 mutation on granule cell composition. Journal of Neurogenetics. [Include actual reference details]