| dc.description.abstract | Alzheimer's Disease (AD) is the leading cause of dementia among elderly individuals. Despite extensive research, the exact
underlying causes of the syndrome remain unknown, hindering the development of effective medications to prevent or alleviate
its progression. In 2021, Biogen introduced aducanumab, a human monoclonal antibody that targets and clears neuritic plaques
(NP) consisting of abnormal protein aggregates formed by amyloid β (Aβ). NP are well-established biomarkers specific to AD
that consistently correlate with synaptic dysfunction, neuroinflammation, and neuronal loss in affected areas. However, clinical
trials demonstrated that aducanumab does not lead to significant cognitive benefits. Despite the ineffectiveness of aducanumab
on cognitive performance, no studies have investigated whether the treatment positively affects other frequently studied AD
biomarkers, such as brain atrophy and the development of white matter hyperintensities (WMHs) associated with white matter
(WM) damage. Examining the impact of the treatment on these structural AD features could provide insight into the role of
NP and shed light on the extent of the effects resulting from their removal. In this study, we conducted a longitudinal
investigation to explore the influence of aducanumab on AD-related atrophy in critical brain regions and the development of
lobar WMHs. We compared the results from a group of aducanumab-treated AD (TAD) patients with those of normal AD
(NAD) patients and individuals with mild cognitive impairment (MCI). Overall, our findings indicate that aducanumab does
not mitigate regional atrophy. However, it effectively slows down the growth and spread of WMH volumes over a two-year
treatment period. These results suggest that aducanumab may help limit WM damage, thereby mitigating the disrupted
connectivity commonly observed in AD brains. This effect could potentially prevent the decline of cognitive abilities that
heavily rely on intact WM, such as working memory. Our study concludes that combination therapy targeting multiple aspects
of AD may be the most effective treatment. | |
