This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research
Fang Li
First Affiliated Hospital of Jinzhou Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4932-1177
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Emerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer disease (AD). The aim of the study was to investigate whether neural-derived plasma exosomal amyloid-β and tau protein levels are associated with OH in diabetes mellitus (DM) patients.
Methods
There were 274 subjects without dementia included in the study: 81 control participants (controls), 101 normotensive patients with DM without OH, and 92 patients with DM and neurogenic OH (DMOH). Neuronal-derived exosomal proteins were measured by ELISA kits for amyloid-β and tau.
Results
The neuronal-derived exosome levels of Aβ42, T-tau, and P-T181-tau in the DM with OH group were higher than those in the DM and control groups. Multivariable linear regression analysis showed that the presence of OH in patients with DM was associated with elevated exosomal Aβ42 (β = 0.172, P = 0.018), T-tau(β = 0.159, P = 0.030), and P-T181-tau (β = 0.220, P = 0.003) levels after adjustment for age, sex, APOE ε4, duration of type 2 diabetes, HbA1c and cardiovascular risk factors. Furthermore, the levels of Aβ42, T-tau, and P-T181-tau in neuronal-derived exosomes were correlated with HIF-1α levels and the drop in mean cerebral blood flow velocity from the supine to upright position.
Conclusions
The presence of OH in DM patients was independently associated with elevated the Aβ42, T-tau, and PT181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.
Trial registration
Chinese Clinical Trial Registry (Identifier: ChiCTR1900021544 ). Registered 27 February 2019.
Keywords
Orthostatic Hypotension, Cognition function, Type 2 Diabetes Mellitus, amyloid-β proteins, tau proteins, exosomes
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 11 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cognitive Neuroscience
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Fang Li
First Affiliated Hospital of Jinzhou Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4932-1177
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 11 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cognitive Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Emerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer disease (AD). The aim of the study was to investigate whether neural-derived plasma exosomal amyloid-β and tau protein levels are associated with OH in diabetes mellitus (DM) patients.
Methods
There were 274 subjects without dementia included in the study: 81 control participants (controls), 101 normotensive patients with DM without OH, and 92 patients with DM and neurogenic OH (DMOH). Neuronal-derived exosomal proteins were measured by ELISA kits for amyloid-β and tau.
Results
The neuronal-derived exosome levels of Aβ42, T-tau, and P-T181-tau in the DM with OH group were higher than those in the DM and control groups. Multivariable linear regression analysis showed that the presence of OH in patients with DM was associated with elevated exosomal Aβ42 (β = 0.172, P = 0.018), T-tau(β = 0.159, P = 0.030), and P-T181-tau (β = 0.220, P = 0.003) levels after adjustment for age, sex, APOE ε4, duration of type 2 diabetes, HbA1c and cardiovascular risk factors. Furthermore, the levels of Aβ42, T-tau, and P-T181-tau in neuronal-derived exosomes were correlated with HIF-1α levels and the drop in mean cerebral blood flow velocity from the supine to upright position.
Conclusions
The presence of OH in DM patients was independently associated with elevated the Aβ42, T-tau, and PT181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.
Trial registration
Chinese Clinical Trial Registry (Identifier: ChiCTR1900021544 ). Registered 27 February 2019.
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Loading...