Journal
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
Volume 5, Issue 2, Pages 162-171Publisher
WILEY
DOI: 10.1002/acn3.518
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Funding
- Swedish Research Council
- Swedish State Support for Clinical Research
- Knut and Alice Wallenberg Foundation
- Torsten Soderberg Foundation
- Frimurarestiftelsen and Swedish Brain Foundation
- Wolfson Foundation
- Alzheimer's Research UK
- National Institute for Health Research Queen Square Dementia Biomedical Research Unit
- National Institute for Health Research University College London Hospital Biomedical Research Centre
- Engineering and Physical Sciences Research Council [EP/J020990/1]
- Medical Research Council [CSUB19166]
- Alzheimer's Research UK [ARUK-Network 2012-6-ICE, ARUK-PG2014-1946]
- European Union's Horizon research and innovation programme [666992]
- Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility
- BRC at the UCL Institute of Neurology
- BRC at the UCLH-National Hospital for Neurology and Neurosurgery, London, UK
- Alzheimers Research UK [ARUK-PG2014-1946] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/J020990/1] Funding Source: researchfish
- Medical Research Council [G116/143, MR/L023784/1, UKDRI-1003, G0401247, UKDRI-1001, G0801306] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10134, CL-2016-18-004] Funding Source: researchfish
- Rosetrees Trust [M668-CD1] Funding Source: researchfish
- EPSRC [EP/J020990/1] Funding Source: UKRI
- MRC [MR/L023784/1, G0801306, G0401247, UKDRI-1001, UKDRI-1003, G116/143] Funding Source: UKRI
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Objective: To assess whether high levels of cerebrospinal fluid neurogranin are found in atypical as well as typical Alzheimer's disease. Methods: Immunoassays were used to measure cerebrospinal fluid neurogranin in 114 participants including healthy controls (n=27), biomarker-proven amnestic Alzheimer's disease (n=68), and the atypical visual variant of Alzheimer's (n=19) according to international criteria. CSF total-tau, A beta 42, and neurofilament light concentrations were investigated using commercially available assays. All affected individuals had T1-weighted volumetric MR images available for analysis of whole and regional brain volumes. Associations between neurogranin, brain volumes, total-tau, A beta 42, and neurofilament light were assessed. Results: Median cerebrospinal fluid neurogranin concentrations were higher in typical and atypical Alzheimer's compared to controls (P<0.001 and P=0.005). Both neurogranin and total-tau concentrations, but not neurofilament light and A beta 42, were higher in typical Alzheimer's compared to atypical patients (P=0.004 and P=0.03). There were significant differences in the left hippocampus and right and left superior parietal lobules in atypical patients, which were larger (P=0.03) and smaller (P=0.001 and P<0.001), respectively, compared to typical patients. We found no evidence of associations between neurogranin and brain volumes but a strong association with total-tau (P<0.001) and a weaker association with neurofilament light (P=0.005). Interpretation: These results show significant differences in neurogranin and total-tau between typical and atypical patients, which may relate to factors other than disease topography. The differential relationships between neurogranin, total-tau and neurofilament light in the Alzheimer's variants, provide evidence for mechanistically distinct and coupled markers of neurodegeneration.
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