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CEREBROSPINAL FLUID AMYLOID BETA 38 ,40, 42 AND 43 LEVELS AS BIOMARKERS FOR SPORADIC AND HEREDITARY CEREBRAL AMYLOID ANGIOPATHY
Abstract
Aims
Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-beta (Aβ) in the cerebral vasculature and has been associated with intracerebral haemorrhages and dementia. CAA diagnosis is based on the identification of lobar (micro-)bleeds and cortical superficial siderosis on MRI. However, these markers are indirect and reflect only late-stage manifestations. We evaluated the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42 and Aβ43 in cerebrospinal fluid (CSF) to discriminate CAA from controls.
Methods
CSF Aβ peptides were quantified in a discovery cohort of sporadic CAA patients (n=27; sCAA) and age-matched controls (n=40), a validation cohort of sCAA patients (n=43) and age-matched controls (n=36), and in a cohort of Dutch-type hereditary CAA (D-CAA) (asymptomatic; n=10, symptomatic; n=12) and age-matched controls (n=22 and n=28, respectively). All comparisons were adjusted for age and sex by linear regression.
Results
In the discovery cohort, we found decreased levels of Aβ38 (p=0.021), Aβ40 (p=0.031), Aβ42 (p<0.0001) and Aβ43 (p<0.0001) in sCAA patients. In the validation cohort, we could confirm decreased levels of Aβ38 (p<0.0001), Aβ40 (p<0.0001), Aβ42 (p<0.0001) and Aβ43 (p<0.0001) in sCAA patients. We also found decreased levels of Aβ38 (p=0.002), Aβ40 (p=0.031), Aβ42 (p<0.0001) and Aβ43 (p=0.001) in asymptomatic D-CAA patients, and in symptomatic D-CAA patients (Aβ38: p<0.0001, Aβ40: p<0.0001, Aβ42: p<0.0001, Aβ43: p<0.0001).
Conclusions
Aβ peptides may have strong potential as biomarkers for the diagnosis of sCAA and D-CAA. In addition, decreased levels of Aβ peptides in asymptomatic D-CAA patients indicate that abnormal Aβ deposition is already present in the preclinical stage.