Post-mortem Proton Magnetic Resonance Spectrometric Measures of Brain Regions in Patients with a Pathological Diagnosis of Alzheimer's Disease and Multi-infarct Dementia

1992 ◽  
Vol 160 (2) ◽  
pp. 187-190 ◽  
Author(s):  
John A. O. Besson ◽  
Philip V. Best ◽  
E. Roy Skinner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Relaxation Times ◽  
Brain Regions ◽  
Pathological Diagnosis ◽  
Tissue Water Content ◽  
Tissue Water ◽  
Spin Lattice

In-vitro spectrometric measures were made of spin-lattice (T1) and spin-spin (T2) relaxation times of samples of grey and white matter from the brains of 15 patients with a pathological diagnosis of Alzheimer's disease, 5 with multi-infarct dementia, and 11 non-demented subjects. Relaxation times were significantly greater in the parietal white matter and temporal white matter of patients with Alzheimer's disease compared with that of the other subjects. This was associated with an increase in tissue water content. These findings confirm measures obtained in some imaging studies.

scholarly journals Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Senthilkumar Sivanesan ◽  
Ravi Mundugaru ◽  
Jayakumar Rajadas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketone Bodies ◽  
Brain Regions ◽  
Pentose Phosphate ◽  
Lactate Shuttle ◽  
Carboxy Terminal ◽  
Brain Energy

Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer’s disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (β-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of β-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aβ is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other β-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

scholarly journals Plasma neurofilament light and cerebrospinal fluid biomarkers are associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes ◽  
Cerebrospinal Fluid Biomarkers

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration largely, and synaptic damage in AD. However, there is no investigation of the association between plasma NFL and white matter microstructure integrity. we have investigated the cross-sectional associations of plasma NFL, CSF tau, p tau, and Aβ with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, CSF total tau, CSF p tau, and as well as CSF Aβ, separately using a partial correlation model controlled for the effect of age, sex and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in different regions. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and for MCI progression to AD.

C-terminal inhibition of tau assembly in vitro and in Alzheimer's disease

2000 ◽  
Vol 113 (21) ◽  
pp. 3737-3745 ◽  
Author(s):  
A. Abraha ◽  
N. Ghoshal ◽  
T.C. Gamblin ◽  
V. Cryns ◽  
R.W. Berry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amino Acids ◽  
Disease Process ◽  
Brain Regions ◽  
Microtubule Binding ◽  
C Terminus ◽  
Microtubule Binding Domain ◽  
Tau Polymerization

Alzheimer's disease (AD) is, in part, defined by the polymerization of tau into paired helical and straight filaments (PHF/SFs) which together comprise the fibrillar pathology in degenerating brain regions. Much of the tau in these filaments is modified by phosphorylation. Additionally, a subset also appears to be proteolytically truncated, resulting in the removal of its C terminus. Antibodies that recognize tau phosphorylated at S(396/404)or truncated at E(391) do not stain control brains but do stain brain sections very early in the disease process. We modeled these phosphorylation and truncation events by creating pseudo-phosphorylation and deletion mutants derived from a full-length recombinant human tau protein isoform (ht40) that contains N-terminal exons 2 and 3 and all four microtubule-binding repeats. In vitro assembly experiments demonstrate that both modifications greatly enhance the rates of tau filament formation and that truncation increases the mass of polymer formed, as well. Removal of as few as 12 or as many as 121 amino acids from the C terminus of tau greatly increases the rate and extent of tau polymerization. However, deletion of an additional 7 amino acids, (314)DLSKVTS(320), from the third microtubule-binding repeat results in the loss of tau's ability to form filaments in vitro. These results suggest that only part of the microtubule-binding domain (repeats 1, 2 and a small portion of 3) is crucial for tau polymerization. Moreover, the C terminus of tau clearly inhibits the assembly process; this inhibition can be partially reversed by site-specific phosphorylation and completely removed by truncation events at various sites from S(320) to the end of the molecule.

scholarly journals Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer’s Disease mouse model brain

2020 ◽  
Author(s):  
Bhargy Sharma ◽  
Joanes Grandjean ◽  
Margaret Phillips ◽  
Ambrish Kumar ◽  
Francesca Mandino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Mouse Brain ◽  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Brain Regions ◽  
Mri Contrast ◽  
Neuroprotective Function

AbstractEndogenous brain proteins can recognize the toxic oligomers of amyloid-β (Aβ) peptides implicated in Alzheimer’s disease (AD) and interact with them to prevent their aggregation. Lipocalin-type Prostaglandin D Synthase (L-PGDS) is a major Aβ-chaperone protein in the human cerebrospinal fluid. Here we demonstrate that L-PGDS detects amyloids in diseased mouse brain. Conjugation of L-PGDS with magnetic nanoparticles enhanced the contrast for magnetic resonance imaging. We conjugated the L-PGDS protein with ferritin nanocages to detect amyloids in the AD mouse model brain. We show here that the conjugates administered through intraventricular injections co-localize with amyloids in the mouse brain. These conjugates can target the brain regions through non-invasive intranasal administration, as shown in healthy mice. These conjugates can inhibit the aggregation of amyloids in vitro and show potential neuroprotective function by breaking down the mature amyloid fibrils.

scholarly journals Plasma neurofilament light is associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam ◽  
Fetemeh Ranjbaran ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration, and synaptic damage in AD. However, few investigations have been carried out on the association between plasma NFL and white matter microstructure integrity. We have investigated the cross-sectional associations of plasma NFL, CSF total tau, phosphorylated tau, and Amyloid β with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, separately using a partial correlation model controlled for the effect of age, sex, and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL negatively correlates with FA and the positive correlation with RD, DA, and MD values in different regions. Our findings showed that plasma NFL is associated with white matter changes and AD-related features, including atrophy and hypometabolism. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and MCI progression to AD.

scholarly journals Amplification, not spreading limits rate of tau aggregate accumulation in Alzheimer’s disease

2020 ◽  
Author(s):  
Georg Meisl ◽  
Yukun Zuo ◽  
Kieren Allinson ◽  
Timothy Rittman ◽  
Sarah DeVos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Regions ◽  
Replication Rate ◽  
Promising Strategy ◽  
Human Brains ◽  
The Brain ◽  
Tau Aggregate ◽  
Rate Of Accumulation

AbstractBoth the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we are able to quantify their replication rate in human brains. Remarkably, we obtain comparable rates in several different datasets, with 5 different methods of tau quantification, from seed amplification assays in vitro to tau PET studies in living patients. Our results suggest that the overall rate of accumulation of tau in neocortical regions is limited not by spreading between brain regions but by local replication, which doubles the number of seeds every ~5 years. Thus, we propose that limiting local replication constitutes the most promising strategy to control tau accumulation during AD.

scholarly journals Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors

2008 ◽  
Vol 197 (2) ◽  
pp. 437-446 ◽  
Author(s):  
S Benvenuti ◽  
P Luciani ◽  
I Cellai ◽  
C Deledda ◽  
S Baglioni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Differentiation ◽  
Thyroid Hormones ◽  
Brain Regions ◽  
Developing Brain ◽  
Neuronal Marker ◽  
Neuronal Precursor Cells ◽  
Neuronal Precursors

Thyroid hormones (TH) play an important role in the development of human brain, by regulating the expression of specific genes. Selective Alzheimer's disease indicator-1 (seladin-1) is a recently discovered gene with neuroprotective properties, which has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 has anti-apoptotic properties mainly due to the inhibition of the activation of caspase 3. The aim of this study was to determine whether seladin-1 may be regarded as a new mediator of the effects of TH in the developing brain. In order to demonstrate this hypothesis, the effects of TH both on cell differentiation and on the expression of seladin-1 were assessed in two different cell models, i.e. fetal human neuroepithelial cells (FNC) and human mesenchymal stem cells (hMSC), which can be differentiated into neurons. 3,3′,5-Triiodothyronine (T3) determined different biological responses (inhibition of cell adhesion, induction of migration, and increase in the expression of the neuronal marker neurofilament-M and Na+ and Ca2+ channel functionality) in both FNC and hMSC, which express TH receptors. Then, we showed that TH significantly increase the expression levels of seladin-1, and that T3 effectively prevents camptothecin-induced apoptosis. However, in hMSC-derived neurons the expression of seladin-1 was not affected by TH. Our results demonstrated for the first time that seladin-1 is a novel TH-regulated gene in neuronal precursors. In view of its anti-apoptotic activity, it might be hypothesized that one of the functions of the increased seladin-1 levels in the developing brain may be to protect neuronal precursor cells from death.

Seeding-Competent Tau in Gray Matter Versus White Matter of Alzheimer’s Disease Brain

2021 ◽  
Vol 79 (4) ◽  
pp. 1647-1659
Author(s):  
Ruozhen Wu ◽  
Jianlan Gu ◽  
Dingwei Zhou ◽  
Yunn Chyn Tung ◽  
Nana Jin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Gray Matter ◽  
Brain Regions ◽  
Hyperphosphorylated Tau ◽  
Tau Hyperphosphorylation ◽  
Brain Extracts ◽  
Axonal Compartment ◽  
Tau Aggregation

Background: Neurofibrillary pathology of abnormally hyperphosphorylated tau spreads along neuroanatomical connections, underlying the progression of Alzheimer’s disease (AD). The propagation of tau pathology to axonally connected brain regions inevitably involves trafficking of seeding-competent tau within the axonal compartment of the neuron. Objective: To determine the seeding activity of tau in cerebral gray and white matters of AD. Methods: Levels of total tau, hyperphosphorylation of tau, and SDS- and β-mercaptoethanol–resistant high molecular weight tau (HMW-tau) in crude extracts from gray and white matters of AD frontal lobes were analyzed by immuno-blots. Tau seeding activity was quantitatively assessed by measuring RIPA buffer–insoluble tau in HEK-293FT/tau151-391 cells treated with brain extracts. Results: We found a comparable level of soluble tau in gray matter versus white matter of control brains, but a higher level of soluble tau in gray matter than white matter of AD brains. In AD brains, tau is hyperphosphorylated in both gray and white matters, with a higher level in the former. The extracts of both gray and white matters of AD brains seeded tau aggregation in HEK-293FT/tau151–391 cells but the white matter showed less potency. Seeding activity of tau in brain extracts was positively correlated with the levels of tau hyperphosphorylation and HMW-tau. RIPA-insoluble tau, but not RIPA-soluble tau, was hyperphosphorylated tau at multiple sites. Conclusion: Both gray and white matters of AD brain contain seeding-competent tau that can template aggregation of hyperphosphorylated tau, but the seeding potency is markedly higher in gray matter than in white matter.

scholarly journals Bundle-specific associations between white matter microstructure and Aβ and tau pathology at their connecting cortical endpoints in older adults at risk of Alzheimer’s disease

2020 ◽  
Author(s):  
Alexa Pichet Binette ◽  
Guillaume Theaud ◽  
François Rheault ◽  
Maggie Roy ◽  
D. Louis Collins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
White Matter ◽  
Free Water ◽  
Brain Regions ◽  
Tau Proteins ◽  
Uncinate Fasciculus ◽  
Preclinical Ad ◽  
White Matter Microstructure

AbstractBeta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer’s disease (AD), are believed to spread through connected regions. Combining diffusion imaging and positron emission tomography, we investigated associations between Aβ, tau and white matter microstructure specifically in bundles connecting brain regions in which AD pathology accumulates. In 126 cognitively normal elderly at risk of AD, we focussed on free-water corrected diffusion measures in the cingulum, posterior cingulum, fornix and uncinate fasciculus. We found higher tissue fractional anisotropy and lower mean and radial diffusivity related to increased Aβ at the cortical endpoints of the cingulum and fornix. We observed similar but stronger associations in the uncinate fasciculus, but with increased Aβ and tau at the endpoints of this bundle. This consistent pattern of associations, with opposite directionality to the usual degeneration pattern in symptomatic individuals, suggests more restricted diffusion in bundles vulnerable to preclinical AD pathology.

Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

2020 ◽  
Vol 18 (4) ◽  
pp. 354-359
Author(s):  
Shirin Tarbiat ◽  
Azize Simay Türütoğlu ◽  
Merve Ekingen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Acetylcholinesterase Activity ◽  
Rosa Damascena ◽  
Free Radical Damage

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

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