In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S2 ( 2020-12)
Abstract:
Cholinergic deficiency is an early and key feature of Alzheimer’s disease (AD). Post‐mortem studies have shown accumulation of pathology and cholinergic cell loss in the nucleus basalis of Meynert (NbM). In‐vivo MRI studies have shown decreased NbM volume and microstructural diffusion changes. We aim to connect the two and assess the direct within‐subject association between local Aβ and (p‐)tau burden with MRI volume and diffusion measures of the NbM, using a post‐mortem MRI‐pathology pipeline. Method Eleven clinical and pathological confirmed AD (6F, 66y±12) and 11 age‐matched non‐neurological donors (6F, 70y±7) underwent post‐mortem in‐situ 3T MRI. T1‐w for anatomical labelling and DTI for quantification of microstructural integrity by measuring fractional anisotropy (FA) and mean diffusivity (MD). Upon subsequent autopsy, the basal forebrain was selected for paraffin embedding and ChAT, Aβ, and (p‐)tau immunohistochemistry. The NbM was identified on MRI and histology based on strict anatomical boundaries. Study outcome measures were NbM MRI T1 volume, FA and MD, as well as ImageJ analyzed ChAT neuron count, Aβ and (p‐)tau area %‐load. Group comparisons were made using non‐parametric tests. MRI‐histology measures were correlated using Spearman’s rho. Result NbM MRI volume was smaller in AD cases than controls (189mm 3 ± 36 vs 229mm 3 ± 49, p=0.03), but no regional difference in FA or MD was found. Compared to controls, AD cases showed higher Aβ (p=0.015) and (p‐)tau (p=0.003) load in the NbM, but no significant difference in ChAT neurons. All cases taken together, correlations between MRI measures and histology showed a negative association between NbM volume and Aβ (rho=‐0.56, p=0.045) and NbM volume and (p‐)tau (rho=‐0.57, p=0.042). Furthermore, a positive association was found between NbM FA and Aβ load (rho=67, p=0.013). Conclusion Compared to controls, an increase in NbM pathology in AD is associated with a decrease in volume without a significant difference in ChAT cell count, leading to compaction of tissue and hence an increase in fractional anisotropy. Further inclusion of cases should shed light on more subtle associations between NbM pathology and MRI measures, such as microstructural changes in cortical projections.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
