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Peer-reviewedCC BY-NCAlzheimer's & dementia (Amsterdam, Netherlands)

Regional amyloid-PET clearance dynamics and anti-Aβ monoclonal antibody therapy: a preliminary real-world study.

  • Alma Ghirelli1,2,3
  • Giordano Cecchetti1,2
  • Edoardo G Spinelli1,2,3
  • Ana Maria Samanes Gajate4
  • Giulia Rugarli1,2,3
  • Stefano Pisano1,2
  • Isabella Aurora Lucilla Zamboni3
  • Elisa Canu1,2
  • Veronica Castelnovo1,2
  • Elisa Sibilla1,2
  • Anna Gilioli1,2
  • Chiara Tripodi1,2,3
6 more authors
  • Fabiola Freri1,2
  • Andrea Panzacchi4
  • Gino Pepe4
  • Arturo Chiti4
  • Massimo Filippi1,2,3,5,6
  • Federica Agosta1,2,3,6
6 affiliations
  1. 1Center for Alzheimer's and Related Diseases (CARD) Neurology Unit IRCCS San Raffaele Scientific Institute Milan Italy.
  2. 2Neuroimaging Research Unit Division of Neuroscience IRCCS San Raffaele Scientific Institute Milan Italy.
  3. 3Vita-Salute San Raffaele University Milan Italy.
  4. 4Nuclear Medicine Service IRCCS San Raffaele Scientific Institute Milan Italy.
  5. 5Neurorehabilitation Unit IRCCS San Raffaele Scientific Institute Milan Italy.
  6. 6Neurotech Hub Vita-Salute San Raffaele University Milan Italy.
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Abstract

Introduction

Amyloid positron emission tomography (PET) is the reference biomarker for treatment target engagement in anti-amyloid beta (Aβ) therapies in early symptomatic Alzheimer's disease (AD), yet global metrics may mask a regional heterogeneity of amyloid clearance.Methods

We report real-world longitudinal amyloid-PET data from 26 patients treated with lecanemab or donanemab for 6 months. Global Centiloids and regional standardized uptake value ratios (SUVRs) were quantified at baseline and 6 months and examined according to treatment, clinical diagnosis, and clinical stage.Results

Amyloid removal was regionally heterogeneous. Patients with mild cognitive impairment showed greater cortical amyloid reduction than those with mild dementia, while early- and late-onset AD exhibited comparable clearance. Frontal, anterior cingulate, and parietal regions showed the largest SUVR reductions, whereas the occipital cortex and temporal mesial cortex were consistently spared, including in patients reaching global amyloid-PET negativity.Discussion

Early amyloid clearance following anti-amyloid treatment is regionally heterogeneous and incompletely captured by global PET measures.

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Cite

BibTeXRIS
BibTeX
@article{ghirelli2026regional,
  title = {{Regional amyloid-PET clearance dynamics and anti-Aβ monoclonal antibody therapy: a preliminary real-world study.}},
  author = {Alma Ghirelli and Giordano Cecchetti and Edoardo G Spinelli and Ana Maria Samanes Gajate and Giulia Rugarli and Stefano Pisano and Isabella Aurora Lucilla Zamboni and Elisa Canu and Veronica Castelnovo and Elisa Sibilla and Anna Gilioli and Chiara Tripodi and Fabiola Freri and Andrea Panzacchi and Gino Pepe and Arturo Chiti and Massimo Filippi and Federica Agosta},
  journal = {Alzheimer's \& dementia (Amsterdam, Netherlands)},
  year = {2026},
  month = oct,
  doi = {10.1002/dad2.70448},
  url = {https://europepmc.org/article/MED/42857419},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Regional amyloid-PET clearance dynamics and anti-Aβ monoclonal antibody therapy: a preliminary real-world study.
AU  - Alma Ghirelli
AU  - Giordano Cecchetti
AU  - Edoardo G Spinelli
AU  - Ana Maria Samanes Gajate
AU  - Giulia Rugarli
AU  - Stefano Pisano
AU  - Isabella Aurora Lucilla Zamboni
AU  - Elisa Canu
AU  - Veronica Castelnovo
AU  - Elisa Sibilla
AU  - Anna Gilioli
AU  - Chiara Tripodi
AU  - Fabiola Freri
AU  - Andrea Panzacchi
AU  - Gino Pepe
AU  - Arturo Chiti
AU  - Massimo Filippi
AU  - Federica Agosta
PY  - 2026
DA  - 2026/10/09
JO  - Alzheimer's & dementia (Amsterdam, Netherlands)
DO  - 10.1002/dad2.70448
UR  - https://europepmc.org/article/MED/42857419
AB  - Introduction  Amyloid positron emission tomography (PET) is the reference biomarker for treatment target engagement in anti-amyloid beta (Aβ) therapies in early symptomatic Alzheimer's disease (AD), yet global metrics may mask a regional heterogeneity of amyloid clearance.Methods  We report real-world longitudinal amyloid-PET data from 26 patients treated with lecanemab or donanemab for 6 months. Global Centiloids and regional standardized uptake value ratios (SUVRs) were quantified at baseline and 6 months and examined according to treatment, clinical diagnosis, and clinical stage.Results  Amyloid removal was regionally heterogeneous. Patients with mild cognitive impairment showed greater cortical amyloid reduction than those with mild dementia, while early- and late-onset AD exhibited comparable clearance. Frontal, anterior cingulate, and parietal regions showed the largest SUVR reductions, whereas the occipital cortex and temporal mesial cortex were consistently spared, including in patients reaching global amyloid-PET negativity.Discussion  Early amyloid clearance following anti-amyloid treatment is regionally heterogeneous and incompletely captured by global PET measures.
SN  - 2352-8729
ER  -