Tau, β-amyloid and β-amyloid precursor protein distribution in the entorhinal-hippocampal alvear and perforant pathways in the Alzheimer’s brain

Shukla, Chinmayee; Bridges, Leslie

doi:10.1016/s0304-3940(01)01719-0

Cited by 17 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abnormalities related to ␤-amyloid [11][12][13][14][15] and the protein Tau 16 -20 in the brain have been the subject of much greater focus, and these factors are thought to play a more central role in AD. [21][22][23][24][25][26][27] Yet, there continues to be support from various lines of clinical research for a link between AD and cerebral microvascular disease as well. 2,6,8,28 -36 Cerebrovascular abnormalities associated with AD have received only limited neuropathological consideration.…”

mentioning

confidence: 99%

Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and APOE Genotype

Stopa

Butala

Salloway

et al. 2008

Stroke

View full text Add to dashboard Cite

Background and Purpose-We examined the associations among the vascular ␤-amyloid levels, smooth muscle actin, wall thickness, and lumen diameter to achieve greater understanding of the arteriolar changes that accompany Alzheimer disease (AD). Methods-Post-mortem pathology brain specimens from 76 patients with AD and 19 non-AD age control subjects were studied. We analyzed arterioles of the frontal cortex (Brodmann area 10) by immunohistochemistry and morphometry, and derived measures of vascular ␤-amyloid level, smooth muscle actin (SMA) volume, and arteriolar wall thickness and lumen diameter. APOE genotype was determined for each case. Results-Overall, there was a striking reciprocal relationship between arteriolar ␤-amyloid volume and smooth muscle actin (PϽ0.0001). In addition, there was a strong positive association between progressively accumulating vascular ␤-amyloid and augmentations in both wall thickness (PϽ0.0001) and lumen width (PϽ0.0001). In comparison with non-AD control subjects, smooth muscle actin was decreased in patients clinically diagnosed with AD and was reduced Ͼ10-fold in cases with AD pathology (Braak I to VI) compared with those lacking AD neuropathology. Significantly altered composition and structure of cortical vessels in pre-Braak stages corroborated our hypothesis that arterioles are devastated early in the AD pathological process. Smooth muscle actin, arteriolar wall thickness, and luminal diameter did not vary with Braak stage severity (PϾ0.05), indicating that substantial arteriolar damage may precede at least some of the interstitial plaques and neuronal tangles. Moreover, the structural and biochemical arteriolar abnormalities did not vary as a function of APOE genotype (PϾ0.05). Conclusion-We postulate that in elderly patients, the continually progressing ␤-amyloid-associated angiopathy, at the arteriolar level, harms the contractile apparatus and cerebral blood flow autoregulation, thereby making the downstream capillaries vulnerable to damage. Collectively, our observations lend further support to the idea that microvascular damage has a role, perhaps relatively early, in the onset of major AD pathology. (Stroke. 2008;39:814-821.)

show abstract

mentioning

confidence: 99%

Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and APOE Genotype

Stopa

Butala

Salloway

et al. 2008

Stroke

View full text Add to dashboard Cite

show abstract

“…The principal input from multimodal association neocortical areas into the hippocampus occurs anteriorly, through the entorhinal cortex, and is known as the perforant pathway (Hyman et al 1984). Numerous lesion studies in experimental animals (for review, see Rolls 2007) show that integrity of the perforant path is a major prerequisite for normal memory function, and disruption of this path, as is known to occur very early in the course of AD, produces profound memory impairment in humans (Hyman et al 1986;García-Sierra 2000;Shukla and Bridges 2001). This functional association was recently supported by in vivo neuroimaging studies in patients with MCI and AD (Kalus et al 2006;Stoub et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Relationships between hippocampal microstructure, metabolism, and function in early Alzheimer’s disease

et al. 2011

View full text Add to dashboard Cite

Abnormal microstructural integrity and glucose metabolism of the hippocampus are common in subjects with Alzheimer's disease (AD) that typically manifest as episodic memory impairment. The above-tissue alterations can be captured in vivo using diffusion tensor imaging (DTI) and positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET). Here, we explored relationships between the above neuroimaging and cognitive markers of early AD-specific hippocampal damage. Twenty patients with early AD (MMSE 25.7 ± 1.7) were studied using DTI and FDG-PET. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). In the between-modality correlation analysis, FDG uptake was strongly associated with diffusivity in the left anterior hippocampus only (r = -0.81, p < 0.05 Bonferroni's corrected for multiple tests). Performance on DVR significantly correlated with left anterior (r = -0.80, p < 0.05) and left mean (r = -0.72, p < 0.05) hippocampal diffusivity, while the correlation with left anterior FDG uptake did not reach statistical significance (r = 0.52, n.s.). DTI-derived diffusivity of the anterior hippocampus might be a sensitive early marker of hippocampal dysfunction as reflected at the synaptic and cognitive levels. This neurobiological distinction of the anterior hippocampus might be related to the disruption of the perforant pathway that is known to occur early in the course of AD.

show abstract

“…In the neocortex (Neo), layers II/III and V gave somewhat more intense signals than the other layers. expression of neprilysin in the perforant pathway may be to counterbalance the active transport of APP in this region [Buxbaum et al, 1998;Phinney et al, 1999] and the resultant generation of Ab [Shukla and Bridges, 2001]. Thus, degradation of Ab by neprilysin is likely to take place at or near synapses and may also proceed inside the secretory vesicles during axonal transport if both APP and neprilysin are colocalized in the same vesicles.…”

Section: Biology and Localization Of Neprilysinmentioning

confidence: 99%

Therapeutic strategies of Alzheimer's disease through manipulation of Aβ metabolism: a focus on Aβ‐degrading peptidase, neprilysin

Fukami

Iwata

Saido

2002

Drug Development Research

View full text Add to dashboard Cite

Deposition of amyloid-b peptide (Ab), a pathological hallmark of Alzheimer's disease (AD), locates upstream of the AD cascade. Ab is constantly anabolized and catabolized in the brain, and the steady-state Ab level is physiologically determined by the metabolic balance between the anabolic and catabolic activities. Even subtle alterations in this metabolic balance over a long period of time could turn Ab into a pathogenic agent that influences both the pathological progression and incidence of the disease. Therefore, AD may be a consequence of proteolytic disorder. In order to overcome AD, lowering the Ab levels in the brain is necessary. There are many strategies to address this, such as b-, g-secretase inhibitors or Ab vaccination. Recently, we demonstrated that neprilysin is the most potent Ab-degrading enzyme in vivo and hypothesized that neprilysin deficiency would influence the steady-state Ab levels in the brain by alternating the Ab metabolism. Therefore, to maintain or upregulate neprilysin activity in the brain will be a relevant strategy for prevention and therapy of AD through reduction of the Ab levels. In this review, we describe several therapeutic strategies for manipulating the Ab level and our current understanding of Ab metabolism, focusing on the Ab-degrading enzyme, neprilysin. Drug Dev.

show abstract

Tau, β-amyloid and β-amyloid precursor protein distribution in the entorhinal-hippocampal alvear and perforant pathways in the Alzheimer’s brain

Cited by 17 publications

References 18 publications

Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and APOE Genotype

Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and APOE Genotype

Relationships between hippocampal microstructure, metabolism, and function in early Alzheimer’s disease

Therapeutic strategies of Alzheimer's disease through manipulation of Aβ metabolism: a focus on Aβ‐degrading peptidase, neprilysin

Contact Info

Product

Resources

About