ArticleNeurology2019
Cortical cholinergic denervation in primary progressive aphasia with Alzheimer pathology.
Article in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Basal Forebrain Volume Predicts Disease Conversion in Prodromal Synucleinopathy.Movement disorders clinical practice · 2026Article
- The cholinergic basal forebrain and its role in neurodegeneration.Journal of neuropathology and experimental neurology · 2025Review
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
- Primary Progressive Aphasia Treatment: Current Treatment Options in Neurology Article Topic: Management of Primary Progressive Aphasia.Current treatment options in neurology · 2025Review
- Efficacy of Acetylcholinesterase Inhibitors in the Logopenic Variant of Primary Progressive Aphasia.Dementia and geriatric cognitive disorders · 2025Article
- Synaptopodin Regulates Denervation-Induced Plasticity at Hippocampal Mossy Fiber Synapses.Cells · 2024Article
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Review
- Resistance of Basal Forebrain Cholinergic Neurons to TDP-43 Proteinopathy in Primary Progressive Aphasia.Journal of neuropathology and experimental neurology · 2022Article
- Structural (dys)connectivity associates with cholinergic cell density in Alzheimer's disease.Brain : a journal of neurology · 2022Article
- miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia.International journal of molecular sciences · 2022Article
- Blood-brain barrier leakage in Alzheimer's disease: From discovery to clinical relevance.Pharmacology & therapeutics · 2022Review
- Protective Effects of a synthetic glycosaminoglycan mimetic (OTR4132) in a rat immunotoxic lesion model of septohippocampal cholinergic degeneration.Glycoconjugate journal · 2022Article
- Article
- Longitudinal Changes in Cognition, Behaviours, and Functional Abilities in the Three Main Variants of Primary Progressive Aphasia: A Literature Review.Brain sciences · 2021Review
- Basal forebrain cholinergic system in the dementias: Vulnerability, resilience, and resistance.Journal of neurochemistry · 2021Review
- New insights into atypical Alzheimer's disease in the era of biomarkers.The Lancet. Neurology · 2021Review
- NGF and Endogenous Regeneration: From Embryology Toward Therapies.Advances in experimental medicine and biology · 2021Article
- GABAergic Inhibitory Interneuron Deficits in Alzheimer's Disease: Implications for Treatment.Frontiers in neuroscience · 2020Review
- Language impairment in primary progressive aphasia and other neurodegenerative diseases.Journal of genetics · 2019Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
objectiveTo investigate the status of the basal forebrain cholinergic system in primary progressive aphasia (PPA) as justification for cholinergic therapy.
methodsA cohort of 36 brains from PPA participants with the neuropathology of Alzheimer disease (PPA-AD, n = 14) or frontotemporal lobar degeneration (PPA-tau, n = 12; PPA-TDP, n = 10) were used for semiquantitative rating of degeneration and gliosis of basal forebrain cholinergic neurons (BFCN). A subpopulation of 5 PPA-AD and 7 control brains underwent detailed analysis of BFCN pathology and cortical cholinergic axonal loss employing immunohistochemical and histochemical methods and stereologic analysis.
resultsSemiquantitatively, 11 (∼80%) PPA-AD participants were rated as having moderate/severe BFCN loss and gliosis, whereas none of the PPA-tau and only 1 (10%) PPA-TDP participant received such a rating. Detailed analysis in the subpopulation of PPA-AD participants revealed substantial tangle formation, loss of BFCN, and degeneration of cortical cholinergic axons. Compared to controls, loss of p75 low affinity neurotrophin receptor-positive BFCN was detected in the PPA-AD participants (
conclusionsOur results demonstrate prominent depletion of BFCN and cortical cholinergic axons in PPA-AD when compared with normal control or other neuropathologic variants of PPA. The demonstration of cholinergic denervation with an anatomy that fits the clinical picture suggests that cholinergic treatment is justified in patients with PPA who have positive AD biomarkers.
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