Hopes for newer Alzheimer’s treatments have been high, yet many have underperformed expectations. A detailed postmortem study published in JAMA offers clues about one discontinued drug. The analysis of a patient who received 30 doses of aducanumab over 4.5 years found that amyloid-beta plaques and tau tangles were cleared only in certain brain areas. Other regions retained heavy deposits linked to cognitive loss. Neuropathologist Edward Lee noted this created a rare comparison of neighboring tissues, revealing how amyloid removal relates to tau buildup and neuron damage. Current therapies mainly target these plaques and tangles, which appear in some but not all dementia cases. While mouse studies showed cognitive gains, human results have been inconsistent. Aducanumab received accelerated FDA approval in 2021 based on early data, but manufacturer Biogen halted production in 2024. The autopsy indicated the antibody reduced plaques mainly in superficial brain layers, with deeper areas largely unaffected. Regions with lower amyloid also showed reduced tau and slower tissue loss, hinting that early plaque removal might limit further damage. Lead author Christopher Brown suggests amyloid remains a viable target if addressed before symptoms emerge. Still, some researchers question whether clearing these proteins directly improves cognition, as they may be markers rather than root causes.
