Onset of Preclinical Alzheimer Disease in Monozygotic Twins.
Aged
Aged, 80 and over
Alzheimer Disease
/ cerebrospinal fluid
Amyloid beta-Peptides
/ cerebrospinal fluid
Apolipoproteins E
/ genetics
Biomarkers
/ cerebrospinal fluid
Depression
/ psychology
Environment
Female
Genotype
Humans
Male
Middle Aged
Neuropsychological Tests
Peptide Fragments
/ cerebrospinal fluid
Positron-Emission Tomography
Twins, Monozygotic
tau Proteins
/ cerebrospinal fluid
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
08
02
2021
received:
16
06
2020
accepted:
10
02
2021
pubmed:
15
2
2021
medline:
27
5
2021
entrez:
14
2
2021
Statut:
ppublish
Résumé
The present work was undertaken to study the genetic contribution to the start of Alzheimer's disease (AD) with amyloid and tau biomarkers in cognitively intact older identical twins. We studied in 96 monozygotic twin-pairs relationships between amyloid-beta (Aβ) aggregation as measured by the Aβ1-42/1-40 ratio in cerebrospinal fluid (CSF; n = 126) and positron emission tomography (PET, n = 194), and CSF markers for Aβ production (beta-secretase 1, Aβ1-40, and Aβ1-38) and CSF tau. Associations among markers were tested with generalized estimating equations including a random effect for twin status, adjusted for age, gender, and apolipoprotein E ε4 genotype. We used twin analyses to determine relative contributions of genetic and/or environmental factors to AD pathophysiological processes. Twenty-seven individuals (14%) had an abnormal amyloid PET, and 14 twin-pairs (15%) showed discordant amyloid PET scans. Within twin-pairs, Aβ production markers and total-tau (t-tau) levels strongly correlated (r range = 0.73-0.86, all p < 0.0001), and Aβ aggregation markers and 181-phosphorylated-tau (p-tau) levels correlated moderately strongly (r range = 0.50-0.64, all p < 0.0001). Cross-twin cross-trait analysis showed that Aβ1-38 in one twin correlated with Aβ1-42/1-40 ratios, and t-tau and p-tau levels in their cotwins (r range = -0.28 to 0.58, all p < .007). Within-pair differences in Aβ production markers related to differences in tau levels (r range = 0.49-0.61, all p < 0.0001). Twin discordance analyses suggest that Aβ production and tau levels show coordinated increases in very early AD. Our results suggest a substantial genetic/shared environmental background contributes to both Aβ and tau increases, suggesting that modulation of environmental risk factors may aid in delaying the onset of AD pathophysiological processes. ANN NEUROL 2021;89:987-1000.
Identifiants
pubmed: 33583080
doi: 10.1002/ana.26048
pmc: PMC8251701
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoproteins E
0
Biomarkers
0
MAPT protein, human
0
Peptide Fragments
0
amyloid beta-protein (1-40)
0
amyloid beta-protein (1-42)
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Twin Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
987-1000Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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