Details

Autor(en) / Beteiligte

• Pascoal, Tharick A.
• Chamoun, Mira
• Lax, Elad
• Wey, Hsiao-Ying
• Shin, Monica
• Ng, Kok Pin
• Kang, Min Su
• Mathotaarachchi, Sulantha
• Benedet, Andrea L.
• Therriault, Joseph
• Lussier, Firoza Z.
• Schroeder, Frederick A.
• DuBois, Jonathan M.
• Hightower, Baileigh G.
• Gilbert, Tonya M.
• Zürcher, Nicole R.
• Wang, Changning
• Hopewell, Robert
• Chakravarty, Mallar
• Savard, Melissa
• Thomas, Emilie
• Mohaddes, Sara
• Farzin, Sarah
• Salaciak, Alyssa
• Tullo, Stephanie
• Cuello, A. Claudio
• Soucy, Jean-Paul
• Massarweh, Gassan
• Hwang, Heungsun
• Kobayashi, Eliane
• Hyman, Bradley T.
• Dickerson, Bradford C.
• Guiot, Marie-Christine
• Szyf, Moshe
• Gauthier, Serge
• Hooker, Jacob M.
• Rosa-Neto, Pedro

Titel

[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease

Ist Teil von

• Nature communications, 2022-07, Vol.13 (1), p.4171-4171, Article 4171

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Abstract Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-β and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-β, tau, and class I histone deacetylase (HDAC I isoforms 1–3), we find that HDAC I levels are reduced in patients with AD. HDAC I PET reduction is associated with elevated amyloid-β PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-β and tau on brain atrophy and cognitive impairment. HDAC I PET reduction is associated with 2-year longitudinal neurodegeneration and cognitive decline. We also find HDAC I reduction in the postmortem brain tissue of patients with AD and in a transgenic rat model expressing human amyloid-β plus tau pathology in the same brain regions identified in vivo using PET. These observations highlight HDAC I reduction as an element associated with AD pathophysiology.