| Title: |
Selective Vulnerability of the Nucleus Basalis of Meynert Among Neuropathologic Subtypes of Alzheimer Disease |
| Authors: |
Al-Shaikh, Fadi S. Hanna; Duara, Ranjan; Crook, Julia E.; Lesser, Elizabeth R.; Schaeverbeke, Jolien; Hinkle, Kelly M.; Ross, Owen A.; Ertekin-Taner, Nilufer; Pedraza, Otto; Dickson, Dennis W.; Graff-Radford, Neill R.; Murray, Melissa E. |
| Source: |
ISSN:2168-6149 ; ISSN:2168-6157 ; Jama Neurology, vol. 77 (2), (225-233. |
| Publisher Information: |
American Medical Association |
| Publication Year: |
2020 |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; CHOLINERGIC INNERVATION; DEFINED SUBTYPES; HUMAN-BRAIN; TAU; ASSOCIATION; FOREBRAIN; PATTERNS; Aged; 80 and over; Alzheimer Disease; Basal Nucleus of Meynert; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Neurofibrillary Tangles; Neurons; Retrospective Studies |
| Description: |
IMPORTANCE: Corticolimbic patterns of neurofibrillary tangle (NFT) accumulation define neuropathologic subtypes of Alzheimer disease (AD), which underlie the clinical heterogeneity observed antemortem. The cholinergic system, which is the target of acetylcholinesterase inhibitor therapy, is selectively vulnerable in AD. OBJECTIVE: To investigate the major source of cholinergic innervation, the nucleus basalis of Meynert (nbM), in order to determine whether there is differential involvement of NFT accumulation or neuronal loss among AD subtypes. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, retrospective abstraction of clinical records and quantitative assessment of NFTs and neuron counts in the nbM was completed in January 2019 at the Mayo Clinic using the Florida Autopsied Multi-Ethnic (FLAME) cohort, which had been accessioned from 1991 until 2015. The FLAME cohort is derived from the deeded autopsy program funded throughout the State of Florida's memory disorder clinic referral services. Of the 2809 consecutively accessioned FLAME cohort, 1464 were identified as neuropathologically diagnosed AD cases and nondemented normal controls available for clinicopathologic assessment. Quantification of NFTs and neuronal density in the anterior nbM was performed blinded to neuropathologic groupings. MAIN OUTCOMES AND MEASURES: Demographic and clinical characteristics, including cognitive decline measured using the Mini-Mental State Examination score (range, 0-30), were evaluated. The anterior nbM was investigated quantitatively for neuronal loss and NFT accumulation. RESULTS: In total, 1361 AD subtypes and 103 nondemented controls were assessed. The median (interquartile range) age at death was 72 (66-80) years in hippocampal sparing (HpSp) AD, 81 (76-86) years in typical AD, and 86 (82-90) years in limbic predominant AD. The median (interquartile range) count per 0.125 mm2 of thioflavin S-positive NFTs was highest in the nbM of HpSp AD (14 [9-20]; n = 163), lower in typical AD (10 [5-16]; n = 937), ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/20.500.12942/704790; https://doi.org/10.1001/jamaneurol.2019.3606; https://pubmed.ncbi.nlm.nih.gov/31657834 |
| DOI: |
10.1001/jamaneurol.2019.3606 |
| Availability: |
https://lirias.kuleuven.be/handle/20.500.12942/704790; https://hdl.handle.net/20.500.12942/704790; https://lirias.kuleuven.be/retrieve/b4396f6d-6adc-4c89-a7d1-0181cae88088; https://doi.org/10.1001/jamaneurol.2019.3606; https://pubmed.ncbi.nlm.nih.gov/31657834 |
| Rights: |
info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.448ED0BF |
| Database: |
BASE |