Clinicopathologic Evaluation of Amyloid Clearance in Alzheimer Disease.
Christopher A Brown, John L Robinson, Sandhitsu R Das et al.
✦ AI-curated · Sources linked
Case in brief
A man in his 50s with mild cognitive impairment and the Alzheimer disease risk-associated p.R47H TREM2 variant received 30 doses of aducanumab (cumulative dose 280 mg/kg) over 4.5 years in a clinical trial. He died four years after his final dose. Autopsy showed patchy amyloid clearance: regions with low residual amyloid had less tau pathology than untreated control regions, while regions with high amyloid burden had tau levels similar to controls. Low-amyloid regions were also associated with slower longitudinal cortical atrophy on MRI (β = -0.50 [95% CI, -0.62 to -0.37]; t = -7.96 and P < .001).
What made this case unusual
Amyloid clearance was spatially uneven: low residual amyloid was preferentially found at gyral crests, whereas high amyloid burden was concentrated in sulcal depths. The autopsy also showed a laminar pattern, with low amyloid in superficial layers but typically high levels in deep cortical layers in some regions.
Diagnostic / clinical pearl
In this case, downstream tau pathology and MRI-measured atrophy differed by regional residual amyloid burden; amyloid clearance was not uniform across cortical regions.
Why it matters
The findings support further study of whether the location and extent of amyloid clearance influence downstream neuropathologic benefit after amyloid-targeting therapy.