Annals of Neurology : Blood-brain barrier disruption, AD and vascular disease are at high risk

Cognitive impairment and dementia affect more than 50 million people worldwide

However, the relationship between BBB disruption and brain pathology in cognitive impairment remains poorly

Hanzhang Lu et al.

The two approaches used in the study were:

1.

2.

The study measured blood-brain barrier function in patients with mild cognitive impairment (MCI), particularly the permeability of the blood-brain barrier to water and albumin molecules, at 2 molecular scales

Determination of the permeability

The study found that BBBs in MCI patients had increased permeability to small molecules such as water, but no increase in permeability to large molecules such as albumin

Relationship between

(A) Mild cognitive impairment (MCI) versus water permeability-surface area product (PS) boxplot of

(B) CSF/serum albumin ratio box diagram

(C) Scatterplot between water PS and memory z-fraction

(D) Scatter plot

Relationship between blood-brain barrier permeability and pathological and vascular risk of Alzheimer's

(A) Scatterplot

(B) Scatterplot

(C) Scatterplot
of CSF/serum albumin ratio to vascular hazard score.

(D) Scatterplot of cerebrospinal fluid/serum albumin ratio to hypercholesterolemia
.

The permeability of the BBB to water is related to the AD markers of CSF Aβ and ptau
.
On the other hand, the permeability of BBB to albumin is associated with vascular risk factors, especially hypercholesterolemia, but not
with AD pathology.
BBB permeability to small molecules, rather than permeability to large molecules, can predict cognitive function
.

The figure above illustrates that leakage of the blood-brain barrier (BBB) can be small and macromolecule-specific
.

(A) Normal BBB
.

(B) BBBs
that have leaks on small molecules (such as water) but no leaks on large molecules.
A black dot indicates a leak point
.
There is a large number of small leaks
in the capillaries.

(C) The blood-brain barrier is a leakage of macromolecules, such as albumin
.
The number of leak points is limited, resulting in a slow leakage of albumin, but they have little effect on water permeability because the leak spots are present in only one branch of the capillary (one-fifth in this case).

The study found that patients with MCI had higher
blood-brain barrier permeability compared to control groups.
Increased permeability to small molecules such as water in cerebrospinal fluid is associated
with decreased levels of Aβ42 and ptau and decreased cognitive function.
On the other hand, changes in the permeability of the blood-brain barrier to macromolecules such as albumin are related
to vascular risk factors.
These findings suggest that blood-brain barrier damage is associated with AD and vascular risk, but its effects can be distinguished
by spatial scale.
The permeability of BBBs to small molecules has a greater impact on
cognitive ability.