Alz Res Therapy: 27-Hydroxycholesterol is closely related to cognitive decline

Alzheimer's disease (AD) is the most common cause of dementia and is considered a multifactorial disease with complex etiology
.

Lipid metabolism plays an important role in AD

cholesterol

In epidemiological studies, elevated circulating cholesterol, especially in middle age, is associated with an increased risk of dementia and AD, through vascular- related pathways (such as atherosclerosis, stroke, and/or decreased cerebral blood flow) or with the brain Potential link to amyloid deposition
.

The link between changes in lipid composition and aging, coupled with recent advances in lipid research in AD, has increased interest in studying lipid profiles, especially cholesterol metabolites as fluid biomarkers of AD

Blood vessel

The blood-brain barrier separates cholesterol from the brain and the periphery, but allows the flow of its oxidized form, namely oxidized sterols, of which 27-hydroxycholesterol (27-OH) is the most abundant one in the periphery
.

Hydroxysterol affects a series of cell functions, and affects a variety of physiological processes, such as cholesterol metabolism, membrane fluidity and intracellular signaling pathways

Hydroxysterol affects a series of cell functions, and affects a variety of physiological processes, such as cholesterol metabolism, membrane fluidity and intracellular signaling pathways

diabetes

Preclinical studies have pointed out several mechanisms of the effect of 27-OH increase on brain function
.

It is worth noting that CYP27A1-over-expressing mice that produce increased levels of 27-OH will have memory impairment.
The reasons include: decreased neuronal glucose uptake, neuronal branch damage and decreased synaptic density, inflammation, and brain and kidney The hormone-angiotensin system is impaired

Cardiovascular management

In this way, Anna Sandebring-Matton and others of the Caroline School of Medicine in Sweden carried out a 27-OH measurement on the serum samples of FINGER participants (n = 47) to explore: (1) 2-year multi-domain life>
.

gray matter volume, cortical thickness and white matter lesions on MRI ( WML), glucose uptake on FDG-PET, and amyloid load on PiB-PET)

In addition, they investigated the association of 27-OH with cognitive and brain imaging markers at baseline
.

The 2-year Finnish Geriatric Intervention Study for the Prevention of Cognitive Impairment and Disability (FINGER) included people at high risk of dementia (60-77 years old) from the general population, but no dementia or substantial cognitive impairment
.

Participants were randomly assigned to a multi-domain intervention (diet, exercise, cognitive training, and vascular risk management) or a control group (general health advice) at a 1:1 ratio

This FINGER exploratory sub-study included 47 participants and measured 27-OH, cognition, brain MRI, brain FDG-PET and PiB-PET
.

Linear regression models were used to assess the cross-sectional and longitudinal links between 27-OH, cognitive, and neuroimaging markers
.

They found that the decrease in 27-OH during the intervention was related to the improvement of cognition (especially memory)
.
This was not observed in the control group
.

The decrease of 27-OH during the intervention period is related to the improvement of cognition (especially memory)
.
This was not observed in the control group
.

The intervention reduced 27-OH, especially among people with the highest 27-OH levels and younger people
.
No association was found between changes in 27-OH levels and neuroimaging markers
.

However, at baseline, higher 27-OH was associated with lower total gray matter and hippocampal volume, as well as lower cognitive scores
.
These associations are not affected by total cholesterol levels
.
Although gender seems to affect the baseline correlation, it does not affect the longitudinal correlation
.

The important significance of this study lies in the findings: 27-OH seems to be not only a marker of dementia/AD risk, but also a marker for the effect of preventive interventions to monitor cholesterol metabolism
.

Original source:
Sandebring-Matton A, Goikolea J, Björkhem I, et al.
27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial.
Alz Res Therapy .
2021;13(1):56.
doi:10.
1186 /s13195-021-00790-y

27-OH seems to be not only a marker of dementia/AD risk, but also a marker for the effectiveness of preventive interventions to monitor cholesterol metabolism
.
27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial.
Alz Res Therapy

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