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-β 1-42 (Aβ) 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 Aβ levels or positive PET with Aβ 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 Aβ deposition is higher than in the general population.

Niemann-Pick Type C 1 (NPC1) and NPC2 gene variability in demented patients with evidence of brain amyloid deposition / F. Sorrentino, A. Arighi, M. Serpente, B. Arosio, M. Arcaro, C. Visconte, E. Rotondo, R. Vimercati, E. Ferri, G.G. Fumagalli, A.M. Pietroboni, T. Carandini, E. Scarpini, C. Fenoglio, D. Galimberti. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 83:3(2021 Sep 28), pp. 1313-1323. [10.3233/JAD-210453]

Niemann-Pick Type C 1 (NPC1) and NPC2 gene variability in demented patients with evidence of brain amyloid deposition

F. Sorrentino
Primo
;
A. Arighi
Secondo
;
M. Serpente;B. Arosio;M. Arcaro;C. Visconte;E. Rotondo;E. Ferri;G.G. Fumagalli;A.M. Pietroboni;T. Carandini;E. Scarpini;C. Fenoglio
Penultimo
;
D. Galimberti
Ultimo
2021

Abstract

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-β 1-42 (Aβ) 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 Aβ levels or positive PET with Aβ 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 Aβ deposition is higher than in the general population.
Amyloid; cerebrospinal fluid; Niemann-Pick Type C; NPC1; NPC2; psychiatric onset; variability; Aged; Amyloid beta-Peptides; Brain; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Niemann-Pick C1 Protein; Peptide Fragments; Phenotype; Positron-Emission Tomography; Vesicular Transport Proteins; Dementia;
Settore BIO/13 - Biologia Applicata
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/902226
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