ArticleAlzheimer's & dementia (New York, N. Y.)
Chronic GCPII (glutamate-carboxypeptidase-II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Region-specific proteomic analysis of aging rhesus macaques following chronic glutamate-carboxypeptidase-II (GCPII) inhibition elucidates potential treatment strategies for sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- An integrated view of the relationships between amyloid, tau, and inflammatory pathophysiology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.Biological psychiatry · 2025Review
- Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation.Frontiers in aging neuroscience · 2025Article
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- Mass spectrometry-guided discovery of novel GCPII inhibitor scaffolds.Frontiers in pharmacology · 2025Article
- Dynamic Network Connectivity: from monkeys to humans.Frontiers in human neuroscience · 2024Review
- Biomarkers associated with the pathogenesis of Alzheimer's disease.Frontiers in cellular neuroscience · 2023Review
- Chronic GCPII (glutamate-carboxypeptidase-II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques.Alzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Introduction: Current approaches for treating sporadic Alzheimer's disease (sAD) focus on removal of amyloid beta 1-42 (Aβ Methods: Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)),Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)). Results: Aged macaques that received 2-MPPA had significantly lower pT217Tau levels in dlPFC and ERC, and had lowered plasma pT217Tau levels from baseline. pT217Tau levels correlated significantly with GCPII activity in dlPFC. Both 2-MPPA- and vehicle-treated monkeys showed cognitive improvement; 2-MPPA had no apparent side effects. Exploratory CSF analyses indicated reduced pS202Tau with 2-MPPA administration, confirmed in dlPFC samples. Discussion: These data provide proof-of-concept support that GCPII inhibition can reduce tau hyperphosphorylation in the primate cortices most vulnerable in sAD. GCPII inhibition may be particularly helpful in reducing the risk of sAD caused by inflammation. These data in nonhuman primates should encourage future research on this promising mechanism. Highlights: Inflammation is a key driver of sporadic Alzheimer's disease.GCPII inflammatory signaling in brain decreases mGluR3 regulation of calcium.Chronic inhibition of GCPII inflammatory signaling reduced pT217Tau in aged monkeys.GCPII inhibition is a novel strategy to help prevent tau pathology at early stages.
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