Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease

• Down syndrome (DS) is caused by trisomy of chromosome 21, which leads to a propensity to develop amyloid beta (A beta) brain pathology in early adulthood followed later by cognitive and behavioral deterioration. Characterization of the A beta pathology is important to better understand the clinical deterioration of DS individuals and to identify interventive strategies. Brain samples from people with DS and Alzheimer's disease (AD), as well as nondemented controls (NDC), were analyzed with respect to different A beta species. Immunohistochemical staining using antibodies towards A beta was also performed. Elevated levels of soluble A beta protofibrils and insoluble A beta x-40 and A beta x-42 in formic acid brain extracts, and elevated immunohistochemical staining of A beta deposits were demonstrated with the antibody BAN2401 (lecanemab) in DS and AD compared with NDC. These data and the promising data in a large phase 2 CE clinical trial with lecanemab suggest that lecanemab may have the potential to preserve cognitive capacity in DS. Lecanemab is currently in a phase 3 CE clinical trial.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

Amyloid beta

Down syndrome

Alzheimer's disease

Antibody therapy

Immunotherapy

Lecanemab

Protofibril

Publication and Content Type

ref (subject category)

art (subject category)