In the Journals

Blood-brain barrier breakdown may indicate early Alzheimer's disease

People with early cognitive dysfunction developed brain capillary damage and blood-brain barrier breakdown in the hippocampus independent of Alzheimer’s disease amyloid-beta and/or tau, according to data published in Nature Medicine.

These findings suggest that leaky capillaries in the brain may predict early onset of Alzheimer’s disease, according to the research.

“If the blood-brain barrier is not working properly, then there is the potential for damage,” Arthur Toga, PhD, director of the University of Southern California Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine, said in a press release. “It suggests the vessels aren’t properly providing the nutrients and blood flow that the neurons need. And you have the possibility of toxic proteins getting in.”

Prior study has shown that neurovascular dysfunction and blood-brain barrier breakdown develop early in Alzheimer’s disease; however, it’s unknown how they impact changes in the Alzheimer’s disease classical biomarkers — amyloid-beta and tau. In this study, researchers examined brain capillary permeability in individuals who were cognitively normal and those with early cognitive dysfunction who were stratified on cerebrospinal fluid (CSF) analysis as either amyloid-beta–positive or amyloid-beta–negative, or tau-positive or tau-negative.

Overall, 161 older adults were involved in the study. After measuring the permeability of capillaries in the brain’s hippocampus, the investigators found a strong association between cognitive impairment and leakage, according to the press release. Analysis revealed that people with the impaired memory had the most leakage in their brain’s blood vessels in the hippocampus regardless of whether they had abnormal amyloid-beta proteins and tau.

“The fact that we’re seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process,” senior author of the study Berislav Zlokovic, MD, PhD, director of the Zilkha Neurogenetic Institute at the University of Southern California Keck School of Medicine, said in a press release. “That was surprising that this blood-brain barrier breakdown is occurring independently.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.

People with early cognitive dysfunction developed brain capillary damage and blood-brain barrier breakdown in the hippocampus independent of Alzheimer’s disease amyloid-beta and/or tau, according to data published in Nature Medicine.

These findings suggest that leaky capillaries in the brain may predict early onset of Alzheimer’s disease, according to the research.

“If the blood-brain barrier is not working properly, then there is the potential for damage,” Arthur Toga, PhD, director of the University of Southern California Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine, said in a press release. “It suggests the vessels aren’t properly providing the nutrients and blood flow that the neurons need. And you have the possibility of toxic proteins getting in.”

Prior study has shown that neurovascular dysfunction and blood-brain barrier breakdown develop early in Alzheimer’s disease; however, it’s unknown how they impact changes in the Alzheimer’s disease classical biomarkers — amyloid-beta and tau. In this study, researchers examined brain capillary permeability in individuals who were cognitively normal and those with early cognitive dysfunction who were stratified on cerebrospinal fluid (CSF) analysis as either amyloid-beta–positive or amyloid-beta–negative, or tau-positive or tau-negative.

Overall, 161 older adults were involved in the study. After measuring the permeability of capillaries in the brain’s hippocampus, the investigators found a strong association between cognitive impairment and leakage, according to the press release. Analysis revealed that people with the impaired memory had the most leakage in their brain’s blood vessels in the hippocampus regardless of whether they had abnormal amyloid-beta proteins and tau.

“The fact that we’re seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process,” senior author of the study Berislav Zlokovic, MD, PhD, director of the Zilkha Neurogenetic Institute at the University of Southern California Keck School of Medicine, said in a press release. “That was surprising that this blood-brain barrier breakdown is occurring independently.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.