
記憶障害は必ずしもアルツハイマー病ではなく、別の神経変性疾患「LANS」の可能性がある。LANS は徐々に進行する記憶障害が主症状で、脳の辺縁系に限局した変性が特徴である。


coremsg

LANS, a memory-affecting syndrome, is often mistaken for Alzheimer's but progresses slowly and primarily affects the limbic system.

Not Alzheimer's: Have You Seen This 'New' Memory Condition?

アルツハイマー病ではない-この-新しい-記憶障害をご存知ですか-


アルツハイマー病ではない：この「新しい」記憶障害をご存知ですか?


title_rewrite


パーキンソン病と dystonia では、基底核出力ニューロンの活動パターンが異なり、それが両疾患の運動症状の違いを反映している。また、両疾患では直接路投射の可塑性にも差異がある。


Background The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology.

Objective Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.

Results GPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate, and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression.

Conclusion We substantiated claims of hyper-versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.

### Competing Interest Statement

The authors have declared no competing interest.

Interrogating basal ganglia circuit function in Parkinson’s disease and dystonia

パーキンソン病と-dystonia-の基底核回路機能の検討


パーキンソン病と dystonia の基底核回路機能の検討



複数硬化症患者の一部では、インテグレーター複合体の活性低下が、非コーディングRNA及びRNA ポリメラーゼIIの制御異常を引き起こし、広範な転写体の変化をもたらす。


HP1α/CBX5 is an epigenetic regulator with a suspected role in multiple sclerosis (MS). Here, using high-depth RNA sequencing on monocytes, we identified a subset of MS patients with reduced CBX5 expression, correlating with progressive stages of the disease and extensive transcriptomic alterations. Examination of rare non-coding RNA species in these patients revealed impaired maturation/degradation of U snRNAs and enhancer-RNAs, indicative of a reduced activity of the Integrator, a complex with suspected links to increased MS risk. At protein-coding genes, compromised Integrator activity manifested in reduced pre-mRNA splicing efficiency and altered expression of genes regulated by RNA polymerase II pause-release. Inactivation of Cbx5 in the mouse mirrored most of these transcriptional defects and resulted in hypersensitivity to Experimental Autoimmune Encephalomyelitis (EAE). Collectively, our observations suggested a major contribution of the Integrator complex in safeguarding against transcriptional anomalies characteristic of MS, with HP1α/CBX5 emerging as an unexpected regulator of this complex’s activity. These findings bring novel insights into the transcriptional aspects of MS and provide potential new criteria in patient stratification.

### Competing Interest Statement

The authors have declared no competing interest.

Defective Integrator activity shapes the transcriptome of patients with multiple sclerosis

複数硬化症患者の転写体に形状を与える欠陥のあるインテグレーター活性


リンビック優位性記憶障害神経変性症候群(LANS)の新しい診断基準が提案された。これにより、アルツハイマー病と誤診されやすい記憶症状の患者に対して、より正確な診断と適切な治療につなげることができる。


Researchers have published clinical criteria for a type of memory loss in older adults that progresses more slowly and has a better prognosis than Alzheimer's disease.

New Criteria Flag Memory Disorder Often Mistaken for AD

アルツハイマー病と誤診されやすい記憶障害の新しい診断基準


アルツハイマー病患者の一部は、MAPK経路を活性化する病原性変異を持つ微小グリア細胞クローンを有しており、それらが神経炎症を引き起こしている。


Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer’s Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both in vitro and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in human, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients.

One-Sentence Summary: A subset of Alzheimer Disease patients carry mutant microglia somatic clones which promote neuro-inflammation.

### Competing Interest Statement

FG has been a paid consultant (no equity) to Third Rock Ventures from 2018 to 2020. Sequencing costs and analysis in this study were covered in part by a SRA between Third Rock venture and MSKCC. This work led to patents PCT/US2022/037893/WO2023004054A1 'Methods and compositions for the treatment of alzheimer's disease' by MSKCC and PCT/US2018/047964 'Kinase mutation-associated neurodegenerative disorders' by MSKCC.

A microglia clonal inflammatory disorder in Alzheimer’s Disease

アルツハイマー病患者の微小グリア細胞における炎症性クローン性障害


51歳女性のハンチントン病の症例報告。進行性の運動障害、認知機能低下、家族歴から診断に至り、遺伝子検査で確定診断された。


Dr Karen E. Anderson provides a brief guide to the diagnosis, evaluation, and management of Huntington disease.

Progressive Motor, Cognitive Decline in 51-Year-Old Woman

51歳女性の進行性運動障害と認知機能低下


ハンチントン病は進行性の神経変性疾患であり、運動、認知、精神症状を特徴とする。早期診断と包括的な治療管理が重要であり、新しい治療法の開発が期待されている。


These five things to know about diagnosis, quality of life, and management in Huntington disease are crucial for effective care of patients with this devastating neurodegenerative condition.

Huntington Disease: 5 Things to Know

ハンチントン病-知っておくべき5つのこと


ハンチントン病: 知っておくべき5つのこと
