Co-twin design in brain imaging—review on biomarkers of Alzheimer's disease

Varjonen, Anni; Schwarz, Claudia; Vuoksimaa, Eero

doi:10.1093/cercor/bhad181

“…Although inclusion in the study was not dependent on the co-twin’s participation, it is expected that full twin pairs will also participate. This will allow studying if the between-family associations are also evident in within-family comparisons and we can identify twin pairs who are discordant for cognition or biomarkers 55…”

Section: Methods and Analysismentioning

confidence: 99%

TWINGEN – protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer’s disease

Vuoksimaa,

Saari,

Aaltonen

et al. 2023

Preprint

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IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among Finnish biobank donors according to TWINGEN study criteria.Methods and analysisA multi-center study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behavior and sleep. A sub-cohort are being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. TWINGEN data will be transferred to Finnish Institute of Health and Welfare (THL) biobank and we aim to further to transfer it to the FinnGen study where it will be combined with health registry data for prediction of AD.Ethics and disseminationThis recall study consists of FTC/THL/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.Article summaryStrengths and limitations of this studyA large sample of individuals is recruited from a representative biobank databaseUsing health registry information, we exclude those with documented AD or other neurological or psychiatric diseases that can affect cognition. Pre-screening limits the sending of unnecessary invitations and saves costsParticipants have up to 48 years of follow-up questionnaire and clinical data from the Finnish Twin Cohort study and these data can be combined with multifaceted Finnish health registry information. Previous genotype data is available in the biobank from all TWINGEN study participants.We assess the feasibility of remote cognitive testing and blood samples in large-scale screening of AD risk, translating to the requirements of intervention trials and clinical practiceLimitations of the study are a lack of gold standard biomarkers (cerebrospinal fluid, positron emission tomography imaging) and neurological examinations

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“…This will allow studying if the between-family associations are also evident in withinfamily comparisons and we can identify twin pairs who are discordant for cognition or biomarkers. 57…”

Section: Aims Data Analysis and Future Directionsmentioning

confidence: 99%

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

Vuoksimaa,

Saari,

Aaltonen

et al. 2024

BMJ Open

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IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysisA multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and disseminationThis recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

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Targeting epigenetic mechanisms in amyloid-β–mediated Alzheimer’s pathophysiology: unveiling therapeutic potential

Li,

Ramalingam,

Li

2024

Neural Regeneration Research

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Alzheimer's disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer's disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer's disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders. These changes, known as epigenetic modifications, also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity. In this context, we highlight recent advances in understanding the roles played by key components of the epigenetic machinery, specifically DNA methylation, histone modification, and microRNAs, in the development of Alzheimer's disease, synaptic function, and activity-dependent synaptic plasticity. Moreover, we explore various strategies, including enriched environments, exposure to non-invasive brain stimulation, and the use of pharmacological agents, aimed at improving synaptic function and enhancing long-term potentiation, a process integral to epigenetic mechanisms. Lastly, we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer's disease. We suggest that addressing Alzheimer's disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

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Co-twin design in brain imaging—review on biomarkers of Alzheimer's disease

Cited by 3 publications

References 78 publications

TWINGEN – protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer’s disease

TWINGEN – protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer’s disease

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

Targeting epigenetic mechanisms in amyloid-β–mediated Alzheimer’s pathophysiology: unveiling therapeutic potential

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