Article
Nutrition & Dietetics
Karel Kalecky, Paula Ashcraft, Teodoro Bottiglieri
Summary: This study explores the alterations in one-carbon metabolism in Alzheimer's disease (AD) and Parkinson's disease (PD), and finds a potential link between levodopa-carbidopa therapy and dementia in PD patients, as well as the correlation between betaine and cognitive score in PD patients.
Article
Geriatrics & Gerontology
Jens D. Mikkelsen, Sif Kaad, Sanjay S. Aripaka, Bente Finsen
Summary: Histological and biochemical analyses have shown neurodegenerative changes in the cerebral cortex of patients with AD, suggesting a loss of synapses. PET imaging of SV2A has demonstrated reduced synapse density in the hippocampus of AD patients. This study found significantly lower UCB-J binding in the frontal cortex of AD patients, which negatively correlated with age, indicating the potential of SV2A as an important biomarker in AD.
NEUROBIOLOGY OF AGING
(2023)
Article
Geriatrics & Gerontology
Francesco Bellanti, Vidyasagar Naik Bukke, Archana Moola, Rosanna Villani, Caterina Scuderi, Luca Steardo, Gianmauro Palombelli, Rossella Canese, Sarah Beggiato, Mario Altamura, Gianluigi Vendemiale, Gaetano Serviddio, Tommaso Cassano
Summary: This study investigated the therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) in 3 x Tg-AD mice. The results showed that um-PEA can improve the complex-I respiration rate and ATPase activity, as well as ATP content in the cortical mitochondria of the mice. However, um-PEA treatment did not improve the mitochondrial bioenergetics impairments and glutamate release in the hippocampus.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Cell Biology
Alexander M. Kulminski, Ethan Jain-Washburn, Elena Loiko, Yury Loika, Fan Feng, Irina Culminskaya, Alzheimer's Disease Neuroimaging Initiative Alzheimers Dis Neuroimaging Initiative
Summary: This study examined the associations of APOE alleles and polygenic profiles with cerebrospinal fluid and plasma biomarkers, revealing differential effects of specific alleles on different biomarkers.
Article
Biology
Meghan E. Wynne, Oluwaseun Ogunbona, Alicia R. Lane, Avanti Gokhale, Stephanie A. Zlatic, Chongchong Xu, Zhexing Wen, Duc M. Duong, Sruti Rayaprolu, Anna Ivanova, Eric A. Ortlund, Eric B. Dammer, Nicholas T. Seyfried, Blaine R. Roberts, Amanda Crocker, Vinit Shanbhag, Michael Petris, Nanami Senoo, Selvaraju Kandasamy, Steven Michael Claypool, Antoni Barrientos, Aliza Wingo, Thomas S. Wingo, Srikant Rangaraju, Allan I. Levey, Erica Werner, Victor Faundez
Summary: This study demonstrates that mitochondria play a role in regulating the secretome, specifically the upregulation of APOE and other secretome components. Disruption of the electron transport chain, either genetically or pharmacologically, leads to the upregulation of APOE transcript, protein, and secretion. These findings suggest that mitochondria act as upstream regulators of APOE-dependent processes and may play a role in neurodegeneration and Alzheimer's disease.
Article
Endocrinology & Metabolism
Jacob M. Basak, Macy Falk, Danae N. Mitchell, Kelley A. Coakley, Nidia Quillinan, James E. Orfila, Paco S. Herson
Summary: Post-stroke cognitive impairment and dementia (PSCID) affects survivors of large vessel cerebral ischemia. The molecular pathways underlying PSCID may overlap with neurodegenerative pathophysiology, specifically involving alterations in amyloid beta (A beta) levels. Using a mouse model, this study shows that soluble A beta levels are significantly increased in the hippocampus after a stroke, along with increased activity of BACE1, an enzyme involved in A beta production. Additionally, treatment with a BACE1 inhibitor improves stroke-induced deficits in synaptic plasticity, suggesting a potential therapeutic target for PSCID.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Clinical Neurology
Gemma Salvado, Daniel Ferreira, Gregory Operto, Irene Cumplido-Mayoral, Eider M. Arenaza-Urquijo, Raffaele Cacciaglia, Carles Falcon, Natalia Vilor-Tejedor, Carolina Minguillon, Colin Groot, Wiesje M. van der Flier, Frederik Barkhof, Philip Scheltens, Rik Ossenkoppele, Silke Kern, Anna Zettergren, Ingmar Skoog, Jakub Hort, Erik Stomrud, Danielle van Westen, Oskar Hansson, Jose Luis Molinuevo, Lars-Olof Wahlund, Eric Westman, Juan Domingo Gispert
Summary: Carrying the APOE ε2 allele is associated with larger gray matter volumes in brain regions affected by AD, providing additional protection against cognitive decline. Homozygotes for the ε2 allele exhibit larger GM volumes in regions related to successful aging.
ALZHEIMERS & DEMENTIA
(2022)
Article
Agriculture, Multidisciplinary
Jian Bao, Zheng Liang, Xiaokang Gong, Yanna Zhao, Mengjuan Wu, Wei Liu, Chenyu Tu, Xiaochuan Wang, Xiji Shu
Summary: This study found that Tangeretin (TAN) exhibits antidementia activity in APPswe/PSEN1dE9 transgenic mice, reducing cognitive impairment, synaptic impairments, and beta-amyloid accumulations. TAN also showed powerful inhibitory activity against beta-secretase, suggesting it as a potential drug for preventing Alzheimer's disease pathology.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Nutrition & Dietetics
Anneloes Martinsen, Rasha N. M. Saleh, Raphael Chouinard-Watkins, Richard Bazinet, Glenn Harden, James Dick, Noemi Tejera, Matthew G. Pontifex, David Vauzour, Anne-Marie Minihane
Summary: The APOE4 genotype is linked to Alzheimer's disease, while DHA is beneficial to the brain. This study found that cocoa flavanols and APOE genotype can influence the uptake and partitioning of DHA from fish oil, but only in the APOE3 gene.
Article
Biochemistry & Molecular Biology
Bibiana C. Mota, Nathan Ashburner, Laura Abelleira-Hervas, Liyueyue Liu, Robertas Aleksynas, Lucio Claudio Rovati, Gianfranco Caselli, Magdalena Sastre
Summary: Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer's disease (AD). In this study, the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD was evaluated. The results showed that CR4056 improved recognition memory, suppressed pro-inflammatory microglia, and restored fibrinogen extravasation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Isha Mhatre-Winters, Aseel Eid, Yoonhee Han, Kim Tieu, Jason R. Richardson
Summary: Sex and APOE4 genotype are important risk factors for Alzheimer's disease, and inflammation plays a significant role in the pathogenesis of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Liling Dong, Chenhui Mao, Caiyan Liu, Jie Li, Xinying Huang, Jie Wang, Dan Lei, Shanshan Chu, Longze Sha, Qi Xu, Bin Peng, Liying Cui, Jing Gao
Summary: This study found that common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF A beta(42), p-tau, or p-tau/A beta(42).
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Inge Tomic, Laura Schwindt, Dominic Helm, Mandy Rettel, Walter Schulz-Schaeffer, Elmar Krause, Jens Rettig, Klaus Fassbender, Yang Liu
Summary: Deficiency of p38 alpha-MAPK in neurons leads to increased retrograde transportation of BACE1 in axons, shifting it from axonal terminals to lysosomes in the cell body, which exacerbates amyloid deposition in the brain of Alzheimer's disease.
Article
Medicine, Research & Experimental
Marika Marino, Lujia Zhou, Melvin Y. Rincon, Zsuzsanna Callaerts-Vegh, Jens Verhaert, Jerome Wahis, Eline Creemers, Lidia Yshii, Keimpe Wierda, Takashi Saito, Catherine Marneffe, Iryna Voytyuk, Yessica Wouters, Maarten Dewilde, Sandra Duque, Cecile Vincke, Yona Levites, Todd E. Golde, Takaomi C. Saido, Serge Muyldermans, Adrian Liston, Bart De Strooper, Matthew G. Holt
Summary: Single domain antibodies (VHHs) have potential therapeutic value for neurological disorders, but their use in the central nervous system is limited by the blood-brain barrier. This study proposes a gene transfer strategy using BBB-crossing AAV-based vectors to deliver VHH directly into the CNS. The results show that AAV-delivered VHH can effectively inhibit BACE1 and improve cognitive performance in an Alzheimer's disease mouse model, providing a novel therapeutic approach for neurodegenerative diseases.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Sofia Toniolo, Francesco Di Lorenzo, Sergio Bernardini, Nicola Biagio Mercuri, Giulia Maria Sancesario
Summary: The definition of Alzheimer's disease (AD) now includes the presence of amyloid (A), tau deposition (T), and neurodegeneration (N) markers as essential for diagnosis. The relationship between blood-brain barrier (BBB) dysfunction and AD-specific biomarkers needs attention as blood-based biomarkers are being used more frequently. Factors such as age, gender, and ApoE status have previously been linked to BBB permeability. In this study, BBB dysfunction was not different across ATN subtypes and was not correlated with cognitive impairment, but patients with BBB disruption had low levels of A beta 40, and ApoE status affected the A beta 42/40 ratio.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Andrew Hooyman, Michael Malek-Ahmadi, Elizabeth B. Fauth, Sydney Y. Schaefer
Summary: The study finds a significant but weak association between grip strength and cognition, cautioning against overinterpretation of this relationship. An alternative motor assessment, functional reaching, is shown to have a stronger and more sensitive relationship with cognition among older adults, providing a potentially more useful measure in clinical settings.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2021)
Article
Neurosciences
Thomas G. Beach, Michael Malek-Ahmadi
Summary: The study found that comorbid neurodegenerative and cerebrovascular diseases are common in Alzheimer's disease dementia (ADD) patients, not only in the elderly but also in early-onset ADD patients. As age increases, the prevalence of certain comorbidities also increases.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Laura J. Mahady, Bin He, Michael Malek-Ahmadi, Elliott J. Mufson
Summary: Telomere attrition was selectively vulnerable within different nodes of the DMN in prodromal AD and in aged NCI individuals with high Braak scores, highlighting a putative role in the pathogenesis of AD.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Jodie B. Nichols, Michael Malek-Ahmadi, Pierre N. Tariot, Geidy E. Serrano, Lucia Sue, Thomas G. Beach
Summary: The study found associations between cerebral amyloid angiopathy and white matter rarefaction with Alzheimer-related neurofibrillary tangle pathology, while microinfarcts and circle of Willis atherosclerosis showed no association. The presence of APOE epsilon 4 carrier status may strengthen the link between white matter rarefaction and neurofibrillary tangle load in Alzheimer's disease.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Geriatrics & Gerontology
Jennifer C. Miguel, Sylvia E. Perez, Michael Malek-Ahmadi, Elliott J. Mufson
Summary: The study found that individuals with DS had higher A beta(42) plaque load in cerebellar neurons compared to those with AD and HC. Protein levels and presence of plaques differed between the groups, with AD and DS showing reductions in certain markers. AD had a significantly higher number of dystrophic axonal swellings compared to DS. Additionally, a strong negative correlation was found between the number of certain interneurons and A beta(42) plaque load.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Kacie Bauer, Michael Malek-Ahmadi
Summary: Findings from several studies suggest that older adults with amnestic mild cognitive impairment (aMCI) perform worse on phonemic fluency tasks, indicating deficits in nonmemory domains. A meta-analysis of 18 studies found that aMCI individuals had significantly lower phonemic fluency performance compared to cognitively unimpaired (CU) individuals. These results highlight the importance of using phonemic fluency tasks in assessing and intervening in aMCI.
APPLIED NEUROPSYCHOLOGY-ADULT
(2023)
Editorial Material
Clinical Neurology
Michael Malek-Ahmadi, Yi Su, Willemijn J. Jansen
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Clara Vila-Castelar, Pierre N. Tariot, Kaycee M. Sink, David Clayton, Jessica B. Langbaum, Ronald G. Thomas, Yinghua Chen, Yi Su, Kewei Chen, Nan Hu, Margarita Giraldo-Chica, Carlos Tobon, Natalia Acosta-Baena, Ernesto Luna, Marisol Londono, Paula Ospina, Victoria Tirado, Claudia Munoz, Eliana Henao, Yamile Bocanegra, Sergio Alvarez, Silvia Rios-Romenets, Valentina Ghisays, Dhruman Goradia, Wendy Lee, Ji Luo, Michael H. Malek-Ahmadi, Hillary D. Protas, Francisco Lopera, Eric M. Reiman, Yakeel T. Quiroz
Summary: This study examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired individuals with and without the Presenilin-1 (PSEN1) E280A mutation. The results suggest that females may have greater cognitive resilience to AD pathology and neurodegeneration than males.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Sydney Y. Schaefer, Michael Malek-Ahmadi, Andrew Hooyman, Jace B. King, Kevin Duff
Summary: Hippocampal atrophy is a common biomarker for Alzheimer's disease, but its use is limited by the cost and contraindications of magnetic resonance imaging (MRI). Recent research has found that a low-cost upper extremity motor task has the potential to identify Alzheimer's disease risk. The study shows that measures of motor task performance can predict hippocampal volume, offering a cost-effective and non-invasive screening method for Alzheimer's disease risk and progression.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Tom Erickson, Michael Malek-Ahmadi, Cecily A. Luft, Cynthia Campbell, Holly K. Strecker
Summary: The ability to quickly express words starting with a specific letter is crucial for assessing language skills and a comprehensive neuropsychological assessment. This study found that using letters M, D, H as a parallel alternative to the standard letters F, A, S in word fluency tests produced similar results, confirming their equivalency.
APPLIED NEUROPSYCHOLOGY-ADULT
(2022)
Article
Neurosciences
Emma C. Utagawa, David G. Moreno, Kristian T. Schafernak, Nicoleta C. Arva, Michael H. Malek-Ahmadi, Elliott J. Mufson, Sylvia E. Perez
Summary: The study revealed the impact of trisomy 21 on postnatal cortical development, including alterations in neuronal migration, neurogenesis, and cellular lamination, which may contribute to cognitive impairment.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Eric M. Reiman, Jeremy J. Pruzin, Silvia Rios-Romenets, Chris Brown, Margarita Giraldo, Natalia Acosta-Baena, Carlos Tobon, Nan Hu, Yinghua Chen, Valentina Ghisays, Jessica Enos, Dhruman D. Goradia, Wendy Lee, Ji Luo, Michael Malek-Ahmadi, Hillary Protas, Ronald G. Thomas, Kewei Chen, Yi Su, Connie Boker, Diego Mastroeni, Sergio Alvarez, Yakeel T. Quiroz, Jessica B. Langbaum, Kaycee M. Sink, Francisco Lopera, Pierre N. Tariot
Summary: This article reports the availability and process of accessing baseline data from the API ADAD trial, highlighting the importance of sharing data to accelerate progress in the field and explore important questions related to AD prevention.
ALZHEIMERS & DEMENTIA
(2023)
Article
Geriatrics & Gerontology
Ida Mohebpour, Michael Malek-Ahmadi, Thomas Virden, Angela Breitmeyer, Marwan N. Sabbagh, Briana Auman, Christine M. Belden, Parichita Choudhury, Autumn Arch, Kathryn Davis, Carol Cline, Naudia Moorley, Alireza Atri, Geidy Serrano, Thomas G. Beach
Summary: This study validated the correlation between the Alzheimer's Questionnaire (AQ) and AD-associated neuritic plaque (NP) and neurofibrillary tangle (NFT) pathology, showing that AQ is highly accurate and reliable for clinicians screening for AD-related cognitive impairment.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Article
Neuroimaging
Valentina Ghisays, Francisco Lopera, Dhruman D. Goradia, Hillary D. Protas, Michael H. Malek-Ahmadi, Yinghua Chen, Vivek Devadas, Ji Luo, Wendy Lee, Ana Baena, Yamile Bocanegra, Edmarie Guzman-Velez, Enmanuelle Pardilla-Delgado, Clara Vila-Castelar, Joshua T. Fox-Fuller, Nan Hu, David Clayton, Ronald G. Thomas, Sergio Alvarez, Alejandro Espinosa, Natalia Acosta-Baena, Margarita M. Giraldo, Silvia Rios-Romenets, Jessica B. Langbaum, Kewei Chen, Yi Su, Pierre N. Tariot, Yakeel T. Quiroz, Eric M. Reiman
Summary: This study utilizes PET measurements to show that cerebellar A beta deposition in CU carriers begins to differ significantly from non-carriers at age 34, 10 years before the estimated onset of mild cognitive impairment. Additionally, cerebellar A beta burden in carriers is associated with age, cortical A beta burden, delayed recall memory, and API ADAD composite score.
NEUROIMAGE-CLINICAL
(2021)
Article
Geriatrics & Gerontology
Zarui A. Melikyan, Michael Malek-Ahmadi, Kathleen O'Connor, Alireza Atri, Claudia H. Kawas, Maria M. Corrada
Summary: This study provided norms and score equivalence for cognitive screening tests for the oldest-old population. The norms for subtests and cognitive domains will aid in evaluating the cognitive status of this group, while the equivalences between different tests will facilitate continuity of cognitive tracking and comparison of studies.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2021)