Review
Clinical Neurology
Gargi Banerjee, John Collinge, Nick C. Fox, Tammaryn Lashley, Simon Mead, Jonathan M. Schott, David J. Werring, Natalie S. Ryan
Summary: Cerebral amyloid angiopathy (CAA) is a significant cerebral small vessel disease that is associated with brain haemorrhage and cognitive change. While the common form affects individuals in mid- to later life, rare early-onset forms are increasingly recognized and may be caused by genetic or iatrogenic factors. This review provides an overview of the causes of early-onset CAA and proposes a structured approach for investigation and management, aiming to raise awareness among healthcare professionals.
Article
Biochemistry & Molecular Biology
Yasuteru Inoue, Masayoshi Tasaki, Teruaki Masuda, Yohei Misumi, Toshiya Nomura, Yukio Ando, Mitsuharu Ueda
Summary: In this study, the researchers found that α-enolase (ENO1) can interact with amyloid beta (Aβ) and inhibit its fibril formation. They also demonstrated that ENO1 can disrupt Aβ fibrils and weaken their cytotoxic effects by degrading Aβ peptides. Additionally, infusion of ENO1 into mouse brains reduced cerebrovascular Aβ deposits and improved cognitive impairment. These findings suggest that ENO1 may be a therapeutic target in cerebral amyloid angiopathy (CAA).
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Cell Biology
Xiaofang Xu, Huikang Xu, Zhaocai Zhang
Summary: Cerebral amyloid angiopathy (CAA) is a disease characterized by the deposition of amyloid beta (A beta) and other amyloid proteins in the brain's blood vessels, leading to cerebrovascular and brain damage. CAA is often associated with cardiac injury, involving A beta, tau, and transthyroxine amyloid (ATTR). A beta acts as the main damaging factor, causing coronary artery atherosclerosis, aortic valve calcification, and cardiomyocyte degeneration. The progression of CAA can further impact the heart through amyloidosis, inflammation, and cerebral hemorrhage. The interaction between CAA and cardiac injury creates a vicious cycle that accelerates the progression of both conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vaibhav Gurunathan, John Hamre, Dmitri K. Klimov, Mohsin Saleet Jafri
Summary: Alzheimer's disease, the most common form of dementia, currently has no cure. This study utilized machine learning techniques and molecular dynamics simulation data to explore the relationship between A beta torsion angles and disease measures. The research has the potential to help determine which specific residues of A beta should be targeted for drug development.
Article
Clinical Neurology
Edgar Chan, Guendalina B. Bonifacio, Corin Harrison, Gargi Banerjee, Jonathan G. Best, Benjamin Sacks, Nicola Harding, Maria del Rocio Hidalgo Mas, H. Rolf Jager, Lisa Cipolotti, David J. Werring
Summary: This study investigated the cognitive function of patients with cerebral amyloid angiopathy (CAA) with and without intracerebral hemorrhage (ICH) and found that cognitive impairment is common in CAA, indicating the potential role of underlying neurodegeneration, possibly related to co-existing Alzheimer's disease pathology.
JOURNAL OF NEUROLOGY
(2023)
Review
Endocrinology & Metabolism
Jenny Szu, Andre Obenaus
Summary: Alzheimer's disease is a devastating neurological disorder characterized by memory and cognitive decline, with two main hypotheses proposed regarding its underlying mechanisms. The amyloid hypothesis suggests A beta accumulation as the basis of AD, while the vascular hypothesis links early vascular damage to increased A beta deposits in the brain. Studies have shown significant morphological changes in the cerebrovasculature associated with AD progression, highlighting the need for further research in this area.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Tsuyoshi Hamaguchi, Kenjiro Ono, Masahito Yamada
Summary: Deposition of amyloid beta protein in the brain is a characteristic of Alzheimer's disease, which can be transmitted between individuals through a prion-like mechanism. Pathological studies have shown that patients with iatrogenic Creutzfeldt-Jakob disease, caused by medical procedures such as human growth hormone injection and dura mater graft, also have cerebral amyloid beta protein deposition. Additionally, young patients with cerebral amyloid angiopathy-related cerebral hemorrhage, who have undergone neurosurgeries with or without dura mater graft in early childhood, suggest that the transmission of cerebral amyloid beta protein pathology is often through amyloid angiopathy rather than parenchymal deposition.
NEUROCHEMICAL RESEARCH
(2022)
Review
Medicine, General & Internal
Mo-Kyung Sin, Edward Zamrini, Ali Ahmed, Kwangsik Nho, Ihab Hajjar
Summary: Anti-amyloid therapies (AATs) are emerging treatments for early Alzheimer's disease (AD). However, they may cause abnormal signals in the brain, known as amyloid-related imaging abnormalities (ARIA). Cerebral amyloid angiopathy (CAA) is a major risk factor for ARIA.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Neurosciences
Tsuyoshi Hamaguchi, Jee Hee Kim, Akane Hasegawa, Ritsuko Goto, Kenji Sakai, Kenjiro Ono, Yoshinori Itoh, Masahito Yamada
Summary: The study found that exogenous A beta seeds from different A beta pathologies induced A beta deposition in the blood vessels rather than the brain parenchyma, which might be the predominant feature of A beta pathology in iatrogenic transmission cases; Contamination of brain tissues from patients with little A beta pathology could lead to iatrogenic transmission of A beta pathology, emphasizing the urgent need for the development of inactivation methods to prevent such transmission.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Qihui Zhang, Xiaobin Zhao, Peng Lei, Hank F. Kung, Zhi Yang, Lin Zhu, Shujing Wang, Hua Zhu, Xiangxi Meng, Yunyun Duan, Li Sun, Jianwei Pan, Ruixue Ma, Haiyan Hong, Xingquan Zhao, Andrew Demchuk, Eric E. Smith, Yongjun Wang
Summary: This study investigated the distribution of the novel PET ligand [68Ga] Ga-p14-032 in patients diagnosed clinically with probable CAA and found that it exhibited stronger cortical retention in CAA patients compared to AD and NC patients. The results suggest that [68Ga] Ga-p14-032 may be a useful tracer for diagnosing CAA by preferentially binding to vascular amyloid.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Riccardo Milani, Lucio Aniello Mazzeo, Daniela Vismara, Ilaria Salemi, Emanuele Dainese, Emanuela Maderna, Elisa Pellencin, Marcella Catania, Nicole Campanella, Giuseppe Di Fede, Giorgio Giaccone, Andrea Salmaggi
Summary: Cerebral amyloid angiopathy (CAA) is a small vessel disease that leads to spontaneous intracerebral hemorrhage (ICH) in the elderly and is strongly associated with Alzheimer's disease (AD). Recently, iatrogenic early-onset CAA has been identified in patients who had a history of traumatic brain injury or other cerebral and extra-cerebral lesions that required neurosurgery or other medical procedures. The transmission of A beta seeds from neurosurgical instruments or exposure to cadaveric dura mater is suspected to be involved.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Editorial Material
Neurosciences
Andreas Charidimou
Summary: Accurate diagnosis of sporadic cerebral amyloid angiopathy (CAA) is crucial for patient management and research. Traditional diagnostic criteria have limitations, so new biomarker-driven approaches, such as the use of cerebrospinal fluid biomarkers (CSF), should be explored. This commentary discusses the application of CSF in CAA diagnosis and provides tips for clinicians on utilizing CSF data for diagnosis.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Itsuki Hasegawa, Yoko Hirayoshi, Shinobu Minatani, Toshikazu Mino, Akitoshi Takeda, Yoshiaki Itoh
Summary: This study explored the in vivo dynamics of amyloid beta (Aβ) in the perivascular space of the cerebral cortex in mice. The researchers observed the accumulation of Aβ in the localized perivascular space and found that transportation along the vessels was slow and associated with changes in shape. The study also confirmed the transportation of Aβ between the cortical surface and the deeper parenchyma through the perivascular space.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Susanne J. van Veluw, Konstantinos Arfanakis, Julie A. Schneider
Summary: Sporadic cerebral small vessel disease is a major cause of cognitive impairment and dementia in aging brains, characterized by brain small vessel abnormalities and frequently coexisting with Alzheimer disease changes. Ex vivo MRI is a powerful tool to bridge the gap in understanding the underlying neuropathology of MRI-detectable SVD abnormalities.
Article
Neurosciences
Nandakumar Nagaraja, Wei-en Wang, Ranjan Duara, Steven T. DeKosky, David Vaillancourt
Summary: This study aimed to evaluate whether cerebral amyloid angiopathy (CAA) pathology mediates hippocampal atrophy in Alzheimer's disease (AD) patients. The results showed that severe CAA was associated with smaller left hippocampal volume on T1-MRI in patients with neuropathologically confirmed AD, and this relationship was dependent on APOE ε4 genotype.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Theresia J. M. Roelofs, Milou Straathof, Annette van der Toorn, Willem M. Otte, Roger A. H. Adan, Rick M. Dijkhuizen
Summary: Eating disorders and obesity are major health issues in Western Society, requiring an understanding of the neural mechanisms underlying their development. The study found that food intake and sucrose tasting can influence functional network organization, potentially explaining specific patterns in feeding behavior.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Isadora Matias, Luan Pereira Diniz, Isabella Vivarini Damico, Ana Paula Bergamo Araujo, Lais da Silva Neves, Gabriele Vargas, Renata E. P. Leite, Claudia K. Suemoto, Ricardo Nitrini, Wilson Jacob-Filho, Lea T. Grinberg, Elly M. Hol, Jinte Middeldorp, Flavia Carvalho Alcantara Gomes
Summary: The reduction of lamin-B1 is a hallmark of senescent astrocytes contributing to nuclear deformations, which are found in aged mouse brains and post-mortem human brain tissue. This study suggests a regional-dependent aging response of human astrocytes in the hippocampus, with implications for impaired astrocyte functions during aging.
Article
Biotechnology & Applied Microbiology
Jessy van Asperen, Daria M. Fedorushkova, Pierre A. J. T. Robe, Elly M. Hol
Summary: This study found that sGFAP levels were significantly elevated in grade-IV glioma patients compared to healthy controls, with a link to tumor volume but no correlation with patient outcome. Additional studies are needed to determine the usefulness of GFAP in body fluids for grade-IV glioma diagnosis and follow-up.
Article
Immunology
Tamar Smit, Paul R. Ormel, Jacqueline A. Sluijs, Lianne A. Hulshof, Jinte Middeldorp, Lot D. de Witte, Elly M. Hol, Vanessa Donega
Summary: Dysregulation of microglial function is involved in Alzheimer's disease pathogenesis, with changes in immune and inflammatory pathways linked to genetic risk factors. Aβ oligomers may induce a protective response rather than an inflammatory profile in vitro.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Neurosciences
Christiaan F. M. Huffels, Lana M. Osborn, Lianne A. Hulshof, Lieneke Kooijman, Lukas Henning, Christian Steinhaeuser, Elly M. Hol
Summary: The study found that in Alzheimer's disease mice, despite localized increased Kir4.1 protein expression in astrocytes surrounding amyloid plaques, this did not lead to dysfunction in Kir4.1 channel. The results suggest that astrocytes in the dentate gyrus of APP/PS1 mice maintain their ability to buffer extracellular K+ to maintain normal neuronal and synaptic function. This indicates that astrocyte Kir4.1 channel dysfunction is likely not involved in the pathogenesis of Alzheimer's disease.
Article
Endocrinology & Metabolism
Pavel Yanev, Geralda A. F. van Tilborg, Annette van der Toorn, Xiangmei Kong, Ann M. Stowe, Rick M. Dijkhuizen
Summary: In this study, a slow-releasing hydrogel loaded with pro-angiogenic factors was injected into the stroke lesion of rats to promote recovery. The hydrogel showed prolonged release of the factors and resulted in significant sensorimotor recovery and increased vascularization in the perilesional cortex. This method supports brain tissue regeneration and functional recovery in the chronic phase post-stroke.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Geriatrics & Gerontology
Lianne A. Hulshof, Leon A. Frajmund, Danny van Nuijs, Denise C. N. van der Heijden, Jinte Middeldorp, Elly M. Hol
Summary: Through a series of memory tests, the researchers determined that the Barnes maze task is better suited for studying subtle learning and memory deficits in 9-month-old APPswe/PS1dE9 mice. The test revealed deficits in spatial memory and cognitive flexibility in the APPswe/PS1dE9 mice compared to wildtype littermates. Additionally, there were no sex-dependent memory deficit differences in this AD mouse model at this age.
NEUROBIOLOGY OF AGING
(2022)
Review
Clinical Neurology
Aladdin Taha, Joaquim Bobi, Ruben Dammers, Rick M. Dijkhuizen, Antje Y. Dreyer, Adriaan C. G. M. van Es, Fabienne Ferrara, Matthew J. Gounis, Bjoern Nitzsche, Simon Platt, Michael H. Stoffel, Victor Volovici, Gregory J. del Zoppo, Dirk J. Duncker, Diederik W. J. Dippel, Johannes Boltze, Heleen M. M. van Beusekom
Summary: Translation of acute ischemic stroke research to the clinical setting remains limited, with only one drug successfully completing the path from experimental study to clinical practice. Large gyrencephalic animal models, such as dogs, swine, sheep, and nonhuman primates, have been recommended to improve the selection of experimental treatments before testing in clinical studies. This review discusses the characteristics of these animal models and aims to facilitate the selection of appropriate models for studying acute ischemic stroke.
Article
Clinical Neurology
Eduardo Candelario-Jalil, Rick M. Dijkhuizen, Tim Magnus
Summary: The role of neuroinflammation in ischemic stroke pathology and its interactions with central nervous system and peripheral immune responses are critically discussed. Neuroinflammation is associated with blood-brain barrier breakdown, neuronal injury, and worse neurological outcomes during acute phase of stroke.
Review
Endocrinology & Metabolism
Dan Huang, Yunlu Guo, Xiaoyu Guan, Lijun Pan, Ziyu Zhu, Zeng'ai Chen, Rick M. Dijkhuizen, Marco Duering, Fang Yu, Johannes Boltze, Peiying Li
Summary: Cognitive impairment (CI) is a significant health concern in aging populations and is often associated with vascular cognitive impairment (VCI). Reduced cerebral blood flow (CBF) plays a critical role in the progression of VCI, and arterial spin labeling (ASL) is a non-invasive MRI technique that can accurately assess CBF. Recent advancements in ASL have improved its usability and led to an increased application in identifying high-risk VCI patients. ASL, when combined with other imaging modalities and biomarkers, shows great potential in early detection and prevention strategies for VCI.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Christiaan F. M. Huffels, Jinte Middeldorp, Elly M. Hol
Summary: Alzheimer's disease is the main cause of dementia cases worldwide, and it affects the individual components of the quad-partite synapse, including presynaptic and postsynaptic processes, as well as astrocyte and microglia functioning. Understanding these effects is crucial for further research.
NEUROCHEMICAL RESEARCH
(2023)
Review
Clinical Neurology
Noa van der Knaap, Bart A. A. Franx, Charles B. L. M. Majoie, Aad van der Lugt, Rick M. Dijkhuizen
Summary: The goal of reperfusion therapy for acute ischemic stroke (AIS) is to restore cerebral blood flow through recanalization of the occluded vessel. However, successful recanalization does not always result in favorable clinical outcome. Post-recanalization perfusion deficits (PRPDs), constituted by cerebral hypo- or hyperperfusion, may contribute to lagging patient recovery rates, but its clinical significance remains unclear.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Clinical Neurology
Jord J. T. Vink, Eline C. C. van Lieshout, Willem M. M. Otte, Ruben P. A. van Eijk, Mirjam Kouwenhoven, Sebastiaan F. W. Neggers, H. Bart van der Worp, Johanna M. A. Visser-Meily, Rick M. M. Dijkhuizen
Summary: Inhibitory repetitive transcranial magnetic stimulation treatment started within 3 weeks after stroke onset promotes upper limb motor recovery, reduces disability and dependence, and leads to earlier discharge from the rehabilitation center.
Article
Endocrinology & Metabolism
Bart A. A. Franx, Geralda A. F. Van Tilborg, Aladdin Taha, Joaquim Bobi, Annette Van der Toorn, Caroline L. Van Heijningen, Heleen M. M. Van Beusekom, Ona Wu, Rick M. Dijkhuizen, CONTRAST Consortium
Summary: In this study, we investigated the effects of recanalization on disease outcome after experimental cerebral ischemia-reperfusion. We found that recanalization resulted in acute-to-subacute lesion volume reductions, particularly in females. Post-ischemic hyperperfusion developed differently in males and females, and had varying effects on disease outcome, depending on the perfusion parameter used.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Review
Neurosciences
Jessy van Asperen, Pierre A. J. T. Robe, Elly M. Hol
Summary: This review describes the expression of GFAP isoforms and discusses the relevance of studying GFAP and its isoforms in disease, with a specific focus on diffuse gliomas.