| 1. |
- Singleton, E. H., et al.
(författare)
-
The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex
- 2022
-
Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. Methods: VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. Results: The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. Discussion: VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.
|
|
| 2. |
- Murray, C. E., et al.
(författare)
-
The presubiculum is preserved from neurodegenerative changes in Alzheimer's disease
- 2018
-
Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 6:62
-
Tidskriftsartikel (refereegranskat)abstract
- In the majority of affected brain regions the pathological hallmarks of Alzheimer's disease (AD) are beta-amyloid (A beta) deposits in the form of diffuse and neuritic plaques, tau pathology in the form of neurofibrillary tangles, neuropil threads and plaque-associated abnormal neurites in combination with an inflammatory response. However, the anatomical area of the presubiculum, is characterised by the presence of a single large evenly distributed 'lake-like' A beta deposit with minimal tau deposition or accumulation of inflammatory markers. Post-mortem brain samples from sporadic AD (SAD) and familial AD (FAD) and two hereditary cerebral amyloid diseases, familial British dementia (FBD) and familial Danish dementia (FDD) were used to compare the morphology of the extracellular proteins deposited in the presubiculum compared to the entorhinal cortex. The level of tau pathology and the extent of microglial activation were quantitated in the two brain regions in SAD and FAD. Frozen tissue was used to investigate the A beta species and proteomic differences between the two regions. Consistent with our previous investigations of FBD and FDD cases we were able to establish that the 'lake-like' pre-amyloid deposits of the presubiculum were not a unique feature of AD but they also found two non-A beta amyloidosis. Comparing the presubiculum to the entorhinal cortex the number of neurofibrillary tangles and tau load were significantly reduced; there was a reduction in microglial activation; there were differences in the A beta profiles and the investigation of the whole proteome showed significant changes in different protein pathways. In summary, understanding why the presubiculum has a different morphological appearance, biochemical and proteomic makeup compared to surrounding brain regions severely affected by neurodegeneration could lead us to understanding protective mechanisms in neurodegenerative diseases.
|
|
