Alzheimers Dementia: The water exchange rate of the blood-brain barrier is highly correlated with the level of amyloid in the cerebrospinal fluid

Alzheimer's disease (AD) is the most common form of dementia, currently affecting more than 6 million Americans
.

Alzheimer's disease is characterized by progressive neuropathological changes decades before the onset of cognitive and clinical decline

Blood vessel

The BBB is composed of non-branched blood vessels that strictly regulate the movement of ions and molecules between the blood and the central nervous system (CNS)
.

The role of BBB is to transport nutrients from the endothelial cavity and protect the central nervous system from pathogens, toxins and inflammation, as well as other functions

The results of post-mortem human brain studies and animal models support the hypothesis that the decrease in water exchange across the BBB may be related to the decrease in Aβ clearance in living humans
.

Testing this hypothesis requires a technique that can measure subtle changes in the exchange rate of water (and potential solutes) on the BBB

However, DCE-MRI may not be suitable for assessing more subtle forms of BBB dysfunction associated with changes in the active transport system, although there may be applications of DCE that can assess perfusion

The kw index represents the ratio of capillary surface area (PSw) to capillary volume (Vc)

For example, DCE Ktrans provides higher spatial resolution
.

In contrast, DP-ASL may provide a more sensitive sign of early BBB dysfunction, because the water exchange rate is 6000 times faster than the exchange rate of gadolinium on the BBB

In this way, Brian T.
Gold of the Sanders-Brown Center on Aging in the United States, among the elderly with normal cognition, explored whether the water exchange rate (kw) across the BBB is related to the cerebrospinal fluid (CSF) biomarker of AD pathology (Aβ42, total tau[t-tau], hyperphosphorylated tau[p-tau]) are related
.

Core hypothesis: In view of the accumulation of Aβ in the interstitium and is believed to be cleared through the BBB-related lymphatic mechanism, kw will be related to CSF ​​Aβ
.

In particular, we predict that low kw will be associated with low levels of CSF Aβ, which reflects the high deposition of Aβ in neuronal plaques

In addition, they assessed the potential relationship between Kw and neuropsychological functions—whether kw is related to the performance of imagery memory and executive function, which are highly correlated with preclinical AD
.

They performed diffusion preparation, arterial spin labeling (DP-ASL) scans of 40 cognitively normal elderly (67-86 years old), which estimated the water exchange rate (kw) across the BBB
.

Participants also underwent CSF sampling and neuropsychological testing

They found that in multiple brain regions (whole brain, frontal lobe, precuneus, parietal lobe, temporal lobe, medial temporal lobe), BBB kw and CSF amyloid β (Aβ) 42 concentration levels were positively correlated
.

BBB kw is positively correlated with the concentration level of CSF amyloid β (Aβ) 42 BBB kw is positively correlated with the concentration level of CSF amyloid β (Aβ) 42

The BBB kw has only a moderate correlation with neuropsychological performance (episodic memory; executive function)
.

These results indicate that the low water exchange rate across the BBB is related to the low CSF Aβ42 concentration
.

kw may be a non-invasive index that promotes the clearance of BBB Aβ, and this possibility should be further verified in future studies

kw may be a non-invasive index that promotes the clearance of BBB Aβ, and this possibility should be further verified in future studies
.
kw may be a non-invasive index that promotes the clearance of BBB Aβ, and this possibility should be further verified in future studies
.

Original Source: Gold BT, Shao X, Sudduth TL, Jicha GA, Wilcock DM, Seago ER, Wang DJJ.
Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults.
Alzheimers Dement.
2021 May 5.
doi: 10.
1002/alz.
12357.
Epub ahead of print.
PMID: 33949773.

Gold BT, Shao X, Sudduth TL, Jicha GA, Wilcock DM, Seago ER, Wang DJJ.
Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults.
Alzheimers Dement.
2021 May 5.
doi: 10.
1002/alz.
12357.
Epub ahead of print.
PMID: 33949773.
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