Heterozygous APOE Christchurch in familial Alzheimer's disease without mutations in other Mendelian genes.
APOE
Alzheimer's disease
Christchurch
early-onset Alzheimer's disease
genetics
mutation
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
15
10
2020
received:
30
07
2020
accepted:
16
10
2020
pubmed:
24
10
2020
medline:
23
2
2022
entrez:
23
10
2020
Statut:
ppublish
Résumé
We present the clinical and neuropathological findings of a patient with early onset Alzheimer's dementia (AD), heterozygous carrier of the rare Apolipoprotein E Christchurch (APOEch) variant. The patient did not harbor any pathogenic mutation in known Mendelian genes related to AD or other neurodegenerative disorders. A sibling of this patient, also carrying the APOEch variant, developed AD at the age of 66 years old. Our data suggest a possible deleterious effect of this variant, which contrast with the protective role that has been previously shown in a subject homozygous for the APOEch with he Paisa PSEN1 mutation.
Substances chimiques
ApoE protein, human
0
Apolipoproteins E
0
Types de publication
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
579-582Informations de copyright
© 2020 British Neuropathological Society.
Références
Wardell MR, Brennan SO, Janus ED, Fraser R, Carrell RW. Apolipoprotein E2-Christchurch (136 Arg-Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia. J Clin Invest. 1987;80:483-490.
Arboleda-Velasquez JF, Lopera F, O'Hare M, et al. Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25:1680-1683.
Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol. 2011;10:213-220.
Shepherd C, McCann H, Halliday GM. Variations in the neuropathology of familial Alzheimer's disease. Acta Neuropathol. 2009;118:37-52.
Greenberg SM, Rebeck GW, Vonsattel JP, Gomez-Isla T, Hyman BT. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol. 1995;38:254-259.
Carmona-Iragui M, Balasa M, Benejam B, et al. Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal-dominant Alzheimer's disease. Alzheimers Dement. 2017;13:1251-1260.
Xiong L, Davidsdottir S, Reijmer YD, et al. Cognitive profile and its association with neuroimaging markers of non-demented cerebral amyloid angiopathy patients in a stroke unit. J Alzheimers Dis. 2016;52:171-178.
Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucl Acid Res. 2019;47:D886-D894.