Niemann-Pick Type C 1 (NPC1) and NPC2 Gene Variability in Demented Patients with Evidence of Brain Amyloid Deposition

被引：10

作者：

Sorrentino, Federica ^{[1
,2
]}

Arighi, Andrea ^{[1
]}

Serpente, Maria ^{[1
,2
]}

Arosio, Beatrice ^{[1
,2
]}

Arcaro, Marina ^{[1
]}

Visconte, Caterina ^{[1
]}

Rotondo, Emanuela ^{[1
]}

Vimercati, Roberto ^{[1
]}

Ferri, Evelyn ^{[1
]}

Fumagalli, Giorgio G. ^{[1
]}

Pietroboni, Anna M. ^{[1
]}

Carandini, Tiziana ^{[1
]}

Scarpini, Elio ^{[1
,2
]}

Fenoglio, Chiara ^{[2
]}

Galimberti, Daniela ^{[1
,2
]}

机构：

[1] Fdn IRCCS Ca Granda, Osped Policlin, Via Francesco Sforza 35, I-20122 Milan, Italy

[2] Univ Milan, Milan, Italy

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2021年 / 83卷 / 03期

关键词：

Amyloid; cerebrospinal fluid; NPC1; NPC2; Niemann-Pick Type C; psychiatric onset; variability; DISEASE TYPE-C; ALZHEIMERS-DISEASE; DIAGNOSTIC-CRITERIA; BEHAVIORAL VARIANT; IDENTIFICATION; MUTATIONS;

D O I：

10.3233/JAD-210453

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Variants in Niemann-Pick Type C genes (NPC1 and NPC2) have been suggested to play a role as risk or disease modifying factors for Alzheimer's disease (AD). Objective: The aim of this study was to analyze NPC1 and NPC2 variability in demented patients with evidence of brain amyloid-beta 1-42 (A beta) deposition and to correlate genetic data with clinical phenotypes. Methods: A targeted Next Generation Sequencing panel was customized to screen NPC1, NPC2, and main genes related to neurodegenerative dementias in a cohort of 136 demented patients with cerebrospinal fluid (CSF) low A beta levels or positive PET with A beta tracer and 200 non-demented geriatric subjects. Results: Seven patients were carriers of NPC variants in heterozygosis. Four of them displayed pathogenic variants previously found in NPC patients and one AD patient had a novel variant. The latter was absent in 200 non-demented elderly subjects. Five of seven patients (70%) exhibited psychiatric symptoms at onset or later as compared with 43% in non-carriers (p > 0.05). Conclusion: The frequency of NPC1 and NPC2 heterozygous variants in patients with CSF evidence of A beta deposition is higher than in the general population.

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收藏

页码：1313 / 1323

页数：11

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