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Comput Biol Med 2021 Jun 1;134:104537. Epub 2021 Jun 1.

School of Electrical Engineering and Computing, The University of Newcastle, NSW 2308, Australia.

Background: Alzheimer's disease (AD) is one of the deadliest diseases in developed countries. Treatments following early AD detection can significantly delay institutionalisation and extend patients' independence. There has been a growing focus on early AD detection using artificial intelligence. Read More

Eur J Med Chem 2021 Jun 2;222:113565. Epub 2021 Jun 2.

Krembil Research Institute, University Health Network, Toronto, Canada; Faculty of Pharmacy, University of Toronto, Ontario, Canada; Faculty of Medicine, University of Toronto, Ontario, Canada; Department of Chemistry, University of Toronto, Ontario, Canada. Electronic address:

β-Amyloid (Aβ) triggered proteopathic and immunopathic processes are a postulated cause of Alzheimer's disease (AD). Monomeric Aβ is derived from amyloid precursor protein, whereupon it aggregates into various assemblies, including oligomers and fibrils, which disrupt neuronal membrane integrity and induce cellular damage. Aβ is directly neurotoxic/synaptotoxic, but may also induce neuroinflammation through the concomitant activation of microglia. Read More

Neuroimage Clin 2021 Jun 4;31:102712. Epub 2021 Jun 4.

Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI; 334 AD, 520 CN). Read More

Neurobiol Dis 2021 Jun 9:105421. Epub 2021 Jun 9.

Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address:

Neurodegenerative disorders like frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are pathologically characterized by toxic protein deposition in the cytoplasm or nucleus of affected neurons and glial cells. Many of these aggregated proteins belong to the class of RNA binding proteins (RBP), and, when mutated, account for a significant subset of familial ALS and FTD cases. Here, we present first genetic evidence for the RBP gene RBM45 in the FTD-ALS spectrum. Read More

Protein Sci 2021 Jun 12. Epub 2021 Jun 12.

Accademia Nazionale dei Lincei and Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Sapienza Università di Roma, Rome, Italy.

Seventy years ago we learned from Chris Anfinsen that the stereochemical code necessary to fold a protein is embedded into its amino acid sequence. In water, protein morphogenesis is a spontaneous reversible process leading from an ensemble of disordered structures to the ordered functionally competent protein; conforming to Aristotle's definition of substance, the synolon of matter and form. The overall process of folding is generally consistent with a two state transition between the native and the denatured protein: not only the denatured state is an ensemble of several structures, but also the native protein populates distinct functionally relevant conformational (sub)states. Read More

FASEB J 2021 Jul;35(7):e21691

Department of Neurology, Saarland University, Homburg/Saar, Germany.

Amyloid β peptide (Aβ) is the major pathogenic molecule in Alzheimer's disease (AD). BACE1 enzyme is essential for the generation of Aβ. Deficiency of p38α-MAPK in neurons increases lysosomal degradation of BACE1 and decreases Aβ deposition in the brain of APP-transgenic mice. Read More

Aging Cell 2021 Jun 12:e13416. Epub 2021 Jun 12.

Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. Read More

FASEB J 2021 Jul;35(7):e21727

Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France.

We previously discovered the implication of membrane-type 5-matrix metalloproteinase (MT5-MMP) in Alzheimer's disease (AD) pathogenesis. Here, we shed new light on pathogenic mechanisms by which MT5-MMP controls the processing of amyloid precursor protein (APP) and the fate of amyloid beta peptide (Aβ) as well as its precursor C99, and C83. We found in human embryonic kidney cells (HEK) carrying the APP Swedish familial mutation (HEKswe) that deleting the C-terminal non-catalytic domains of MT5-MMP hampered its ability to process APP and release the soluble 95 kDa form (sAPP95). Read More

Nat Rev Neurol 2021 Jun 11. Epub 2021 Jun 11.

Neurology Clinic, Department of Medicine and Surgery, University of Perugia - S. Maria della Misericordia Hospital, Perugia, Italy.

People with epilepsy - in particular, late-onset epilepsy of unknown aetiology - have an elevated risk of dementia, and seizures have been detected in the early stages of Alzheimer disease (AD), supporting the concept of an epileptic AD prodrome. However, the relationship between epilepsy and cognitive decline remains controversial, with substantial uncertainties about whether epilepsy drives cognitive decline or vice versa, and whether shared pathways underlie both conditions. Here, we review evidence that amyloid-β (Aβ) forms part of a shared pathway between epilepsy and cognitive decline, particularly in the context of AD. Read More

NPJ Parkinsons Dis 2021 Jun 11;7(1):50. Epub 2021 Jun 11.

Neurology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.

Long-term effects of continuous subcutaneous apomorphine infusion (CSAI) on health-related quality of life (HRQoL) and predictors of CSAI discontinuation are poorly known. Data from consecutive advanced Parkinson's disease patients treated in routine care were retrospectively collected over 24 months after CSAI initiation, with a focus on the 39-item Parkinson's disease questionnaire (PDQ-39). We determined predictors of CSAI discontinuation and HRQoL improvement using multiple regression analysis. Read More

Clin Genitourin Cancer 2021 May 17. Epub 2021 May 17.

Department of Urology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx NY. Electronic address:

Background: The immune system plays an important role in the pathogenesis of Alzheimer disease (AD), but it remains unclear whether bacillus Calmette-Guérin (BCG) may affect the risk of AD or not.

Methods: Using retrospective chart review, we collected data regarding demographics, comorbidities, cancer diagnosis, BCG treatment, and subsequent diagnosis of AD or other dementia in a racially/ethnically diverse cohort of patients with non-muscle-invasive bladder cancer (NIMBC) receiving treatment between 1984 and 2020 in the Bronx, New York. We used Cox proportional hazard models to examine association between BCG treatment and risk of incident AD or other dementia, adjusting for age, gender, race/ethnicity, and major comorbidities. Read More

Int J Med Inform 2021 Jun 4;153:104513. Epub 2021 Jun 4.

Menzies Health Institute Queensland, Griffith University, Brisbane, Australia; Australian Aged Care Technologies Collaborative, Griffith University, Brisbane, Australia. Electronic address:

Objectives: To map the current state-of-knowledge about the effectiveness of smart home technologies to support the health outcomes of community-dwelling older adults living with dementia.

Design: A scoping review following the methodological frameworks described by Arksey and O'Malley (2005) and Levac et al. (2010). Read More

Eur J Med Chem 2021 May 25;222:113541. Epub 2021 May 25.

Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University (SJTU), Shanghai, China; SJTU-Agilent Technologies Joint Laboratory for Pharmaceutical Analysis, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China; Academy of Pharmacy, Xi'an Jiaotong - Liverpool University, Suzhou, 215123, China. Electronic address:

A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Aβ antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Aβ antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Aβ peptides binding to the cell membrane. Read More

Neuroimage 2021 Jun 9;238:118214. Epub 2021 Jun 9.

Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK; Clinical Neurosciences, North Bristol NHS Trust, Bristol, UK.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Read More

Aging (Albany NY) 2021 Jun 11;13. Epub 2021 Jun 11.

Department of Clinical Research and Innovation, Foch Hospital, Suresnes, France.

SARS-CoV-2 more readily affects the elderly, especially as they present co-morbidities. In the COVID-19 pathogeny, ACE2 appears to be the key cell receptor for SARS-CoV-2 to infect humans. The level of ACE2 gene expression influences the susceptibility of contracting SARS-CoV-2. Read More

Alzheimers Dement 2021 Jun;17(6):917-919

Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.

Brain 2021 Jun 11. Epub 2021 Jun 11.

Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Dementia with Lewy bodies (DLB) is neuropathologically defined by the presence of α-synuclein aggregates, but many DLB cases show concurrent Alzheimer's disease (AD) pathology in the form of β-amyloid plaques and tau neurofibrillary tangles. The first objective of this study was to investigate the effect of AD co-pathology on functional network changes within the default mode network (DMN) in DLB. Secondly, we studied how the distribution of tau pathology measured with PET relates to functional connectivity in DLB. Read More

J Nutr 2021 Jun 10. Epub 2021 Jun 10.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Background: Vitamin D is critical to brain health and a promising candidate to prevent cognitive decline and onset of Alzheimer disease (AD), although the underlying brain mechanisms are unclear.

Objectives: This study aimed to determine the association between vitamin D intake and brain cortical thickness in older adults.

Methods: This was a cross-sectional investigation of 263 cognitively unimpaired participants, aged 65 y and older, participating in the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) trial (an ongoing study testing the effects of a 3-y diet intervention on cognitive decline). Read More

J Alzheimers Dis Rep 2021 Apr 29;5(1):337-343. Epub 2021 Apr 29.

Department of Internal Medicine (Section of Cardiovascular Medicine), Providence VA Medical Center, Providence, RI, USA.

Background: While an association between atherosclerosis and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and cognitive impairment (CI).

Objective: We sought to determine whether AVC derived from lung cancer screening CT (LCSCT) was associated with CI in a moderate-to-high atherosclerotic risk cohort.

Methods: This was a single site, retrospective analysis of 1401 U. Read More

J Alzheimers Dis Rep 2021 Apr 29;5(1):321-336. Epub 2021 Apr 29.

Eli Lilly and Company, Indianapolis, IN, USA.

Background: LY3202626 is a small molecule inhibitor of β-site amyloid precursor protein cleaving enzyme (BACE)1 shown to reduce amyloid-β (Aβ) and Aβ concentrations in plasma and cerebrospinal fluid developed for the treatment of Alzheimer's disease (AD).

Objective: To assess the change from baseline in flortaucipir positron emission tomography (PET) after treatment with LY3202626 compared with placebo in patients with mild AD dementia.

Methods: Patients received daily 3 mg or 12 mg doses of LY3202626 or placebo for 52 weeks. Read More

J Alzheimers Dis Rep 2021 Apr 29;5(1):311-320. Epub 2021 Apr 29.

Department of Neuroscience, Medical School, University of Sheffield, Sheffield, UK.

Background: The presence of recurrent, complex visual hallucinations (VH) is among the core clinical features of dementia with Lewy bodies (DLB). It has been proposed that VH arise from a disrupted organization of functional brain networks. However, studies are still limited, especially investigating the resting-state functional brain features underpinning VH in patients with dementia. Read More

J Alzheimers Dis Rep 2021 Apr 23;5(1):295-310. Epub 2021 Apr 23.

Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.

Background: Parkinson's disease (PD) is one of the most important neurodegenerative disorders in human in which recovery of functions could be achieved by improving the survival and function of residual dopaminergic neurons in the substantia nigra pars compacta. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway.

Objective: Earlier our laboratory has shown that sodium benzoate (NaB), a metabolite of cinnamon and an FDA-approved drug against urea cycle disorders and glycine encephalopathy, increases neuroprotective molecules and protects dopaminergic neurons in a mouse model of PD. Read More

J Alzheimers Dis Rep 2021 Apr 9;5(1):283-294. Epub 2021 Apr 9.

The Birchall Centre, Lennard-Jones Laboratories, Keele University, Keele, Staffordshire, UK.

Background: Familial Alzheimer's disease (fAD) is driven by genetic predispositions affecting the expression and metabolism of the amyloid-β protein precursor. Aluminum is a non-essential yet biologically-reactive metal implicated in the etiology of AD. Recent research has identified aluminum intricately and unequivocally associated with amyloid-β in senile plaques and, more tentatively, co-deposited with neuropil-like threads in the brains of a Colombian cohort of donors with fAD. Read More

J Alzheimers Dis Rep 2021 Apr 6;5(1):275-282. Epub 2021 Apr 6.

Department of Life Sciences, Manchester Metropolitan University, Manchester, UK.

Background: The ɛ4 allele is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD). The neighboring gene has also been implicated in AD due to its close proximity to .

Objective: Here we tested whether methylation of the locus may influence ApoE protein levels and AD pathology. Read More

J Alzheimers Dis Rep 2021 Apr 6;5(1):263-274. Epub 2021 Apr 6.

Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.

Background: Emerging evidence indicates that the misfolded tau protein can propagate aggregates between cells in a prion-like manner. This prion activity has been typically studied in brain extracts of patients with Alzheimer's disease (AD), but not in the olfactory region that can be a potential biomarker in AD.

Objective: To investigate the prion seeding activity of tau in nasal mucosa tissues using a cell culture model of tau propagation. Read More

J Alzheimers Dis Rep 2021 Apr 6;5(1):243-261. Epub 2021 Apr 6.

Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico, Rome, Italy.

Increasing evidence coming from both experimental and humans' studies strongly suggest the existence of a link between epilepsy, in particular temporal lobe epilepsy (TLE), and Alzheimer's disease (AD). Patients with mild cognitive impairment and AD are more prone to have seizures, and seizures seem to facilitate amyloid-β and tau deposits, thus promoting neurodegenerative processes. Consistent with this view, long-lasting drug-resistant TLE and AD have been shown to share several pathological and neuroimaging features. Read More

J Alzheimers Dis Rep 2021 Apr 6;5(1):237-241. Epub 2021 Apr 6.

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Alzheimer's disease (AD) has been associated with periodontitis, which starts as gingivitis. Similar to periodontitis, gingivitis bacteria, bacterial products, and inflammatory mediators can travel to the brain via the blood stream and promote brain inflammation. Periodontal pathogens such as and both associated with AD, have been found in dental plaque of children already at the age of 3. Read More

J Alzheimers Dis Rep 2021 Apr 6;5(1):229-235. Epub 2021 Apr 6.

Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden.

Background: Amyloid-β (Aβ), the key constituent of Alzheimer's disease (AD) plaques, has antimicrobial properties.

Objective: To investigate the association between plasma Aβ and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and .

Methods: Plasma from 339 AD cases, obtained on average 9. Read More

Mol Psychiatry 2021 Jun 10. Epub 2021 Jun 10.

Neuroscience Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD - P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. Read More

Nat Rev Drug Discov 2021 Jun 10. Epub 2021 Jun 10.