Faculty Opinions recommendation of Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds.

Accumulation of amyloid-beta (Aβ) in the brain is thought to derive from the impairment of Aβ clearance mechanisms rather than from its overproduction, which consequently contributes to the development of Alzheimer’s disease. The choroid plexus epithelial cells constitute an important clearance route for Aβ, either by facilitating its transport from the cerebrospinal fluid to the blood, or by synthesizing and secreting various proteins involved in Aβ degradation. Impaired choroid plexus synthesis, secretion, and transport of these Aβ-metabolizing enzymes have been therefore associated with the disruption of Aβ homeostasis and amyloid load. Factors such as aging, female gender, and circadian rhythm disturbances are related to the decline of choroid plexus functions that may be involved in the modulation of Aβ-clearance mechanisms. In this study, we investigated the impact of age, sex hormones, and circadian rhythm on the expression of Aβ scavengers such as apolipoprotein J, gelsolin, and transthyretin at the rat choroid plexus. Our results demonstrated that mRNA expression and both intracellular and secreted protein levels of the studied Aβ scavengers are age-, sex-, and circadian-dependent. These data suggest that the Aβ-degradation and clearance pathways at the choroid plexus, mediated by the presence of Aβ scavengers, might be compromised as a consequence of aging and circadian disturbances. These are important findings that enhance the understanding of Aβ-clearance-regulating mechanisms at the blood–cerebrospinal fluid barrier.

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O4-06-05: Aβ immunization in old mouse lemur primates induces cerebral microhemorrhages and accelerates age-associated iron deposits in the choroid plexus

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1668 ◽

2012 ◽

Vol 8 (4S_Part_17) ◽

pp. P626-P626

Author(s):

Olene Dorieux ◽

Nelly Joseph-Mathurin ◽

Stéphanie Trouche ◽

Audrey Kraska ◽

Mathieu Santin ◽

...

Keyword(s):

Choroid Plexus ◽

Mouse Lemur ◽

Iron Deposits ◽

Cerebral Microhemorrhages

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Assessment of cerebral microbleeds by susceptibility-weighted imaging in Alzheimer’s disease patients: A neuroimaging biomarker of the disease

The Neuroradiology Journal ◽

10.1177/1971400916689483 ◽

2017 ◽

Vol 30 (4) ◽

pp. 330-335 ◽

Cited By ~ 12

Author(s):

Gianvincenzo Sparacia ◽

Francesco Agnello ◽

Giuseppe La Tona ◽

Alberto Iaia ◽

Federico Midiri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Decline ◽

Amyloid Beta ◽

Cerebral Microbleeds ◽

Susceptibility Weighted Imaging ◽

Phosphorylated Tau ◽

Protein Levels ◽

Phosphorylated Tau 181

Purpose The objective of this study was to correlate the presence and distribution of cerebral microbleeds in Alzheimer’s disease patients with cerebrospinal fluid biomarkers (amyloid-beta and phosphorylated tau 181 protein levels) and cognitive decline by using susceptibility-weighted imaging magnetic resonance sequences at 1.5 T. Material and methods Fifty-four consecutive Alzheimer’s disease patients underwent brain magnetic resonance imaging at 1.5 T to assess the presence and distribution of cerebral microbleeds on susceptibility-weighted imaging images. The images were analyzed in consensus by two neuroradiologists, each with at least 10 years’ experience. Dementia severity was assessed with the Mini-Mental State Examination score. A multiple regression analysis was performed to assess the associations between the number and location of cerebral microbleed lesions with the age, sex, duration of the disease, cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels, and cognitive functions. Results A total of 296 microbleeds were observed in 54 patients; 38 patients (70.4%) had lobar distribution, 13 patients (24.1%) had non-lobar distribution, and the remaining three patients (5.6%) had mixed distribution, demonstrating that Alzheimer’s disease patients present mainly a lobar distribution of cerebral microbleeds. The age and the duration of the disease were correlated with the number of lobar cerebral microbleeds ( P < 0.001). Cerebrospinal fluid amyloid-beta, phosphorylated tau 181 protein levels, and cognitive decline were correlated with the number of lobar cerebral microbleeds in Alzheimer’s disease patients ( P < 0.001). Conclusion Lobar distribution of cerebral microbleeds is associated with Alzheimer’s disease and the number of lobar cerebral microbleeds directly correlates with cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels and with the cognitive decline of Alzheimer’s disease patients.

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DEEPMIR: a deep neural network for differential detection of cerebral microbleeds and iron deposits in MRI

Scientific Reports ◽

10.1038/s41598-021-93427-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tanweer Rashid ◽

Ahmed Abdulkadir ◽

Ilya M. Nasrallah ◽

Jeffrey B. Ware ◽

Hangfan Liu ◽

...

Keyword(s):

Neural Network ◽

Deep Learning ◽

Basal Ganglia ◽

Brain Aging ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

Manual Annotation ◽

Average Sensitivity ◽

Convenience Sample ◽

Iron Deposits

AbstractLobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84–0.88 and 0.40–0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75–0.81 and 0.62–0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies.

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Organization of tight junctions in the choroid plexus epithelium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082546 ◽

1978 ◽

Vol 36 (2) ◽

pp. 336-337

Author(s):

B. Van Deurs ◽

J. K. Koehler

Keyword(s):

Choroid Plexus ◽

Present Report ◽

Freeze Fracture ◽

Barrier Properties ◽

Cell Junctions ◽

Structural Basis ◽

Apical Surface ◽

Choroid Plexus Epithelium ◽

Solid Nitrogen ◽

Special Composition

The choroid plexus epithelium constitutes a blood-cerebrospinal fluid (CSF) barrier, and is involved in regulation of the special composition of the CSF. The epithelium is provided with an ouabain-sensitive Na/K-pump located at the apical surface, actively pumping ions into the CSF. The choroid plexus epithelium has been described as “leaky” with a low transepithelial resistance, and a passive transepithelial flux following a paracellular route (intercellular spaces and cell junctions) also takes place. The present report describes the structural basis for these “barrier” properties of the choroid plexus epithelium as revealed by freeze fracture.Choroid plexus from the lateral, third and fourth ventricles of rats were used. The tissue was fixed in glutaraldehyde and stored in 30% glycerol. Freezing was performed either in liquid nitrogen-cooled Freon 22, or directly in a mixture of liquid and solid nitrogen prepared in a special vacuum chamber. The latter method was always used, and considered necessary, when preparations of complementary (double) replicas were made.

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Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

Essays in Biochemistry ◽

10.1042/bse0380037 ◽

2002 ◽

Vol 38 ◽

pp. 37-49 ◽

Cited By ~ 27

Author(s):

Janelle Nunan ◽

David H Small

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Alternative Pathway ◽

Protein A ◽

Proteolytic Processing ◽

Gamma Secretase ◽

Amyloid Beta Protein ◽

Protein Precursor ◽

Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

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