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  1. Article: Editorial: Infection, inflammation, and neurodegeneration: A critical path to Alzheimer's disease, Volume II.

    Mancuso, Roberta / Agostini, Simone / Appelt, Denah M / Balin, Brian J

    Frontiers in aging neuroscience

    2022  Volume 14, Page(s) 1044047

    Language English
    Publishing date 2022-10-06
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2022.1044047
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  2. Article ; Online: Herpes viruses and Alzheimer's disease: new evidence in the debate.

    Balin, Brian J / Hudson, Alan P

    The Lancet. Neurology

    2018  Volume 17, Issue 10, Page(s) 839–841

    MeSH term(s) Alzheimer Disease/etiology ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Alzheimer Disease/virology ; Amyloid beta-Peptides/metabolism ; Herpesviridae/metabolism ; Herpesviridae/pathogenicity ; Herpesviridae Infections/complications ; Herpesviridae Infections/metabolism ; Humans
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2018-09-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2079704-7
    ISSN 1474-4465 ; 1474-4422
    ISSN (online) 1474-4465
    ISSN 1474-4422
    DOI 10.1016/S1474-4422(18)30316-8
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  3. Article ; Online: Intriguing Mixed Pathologic Features in a Case of Dementia With Lewy Bodies.

    Balin, Brian J / Hammond, Christine J / Galluzzi, Katherine E

    The Journal of the American Osteopathic Association

    2019  Volume 119, Issue 9, Page(s) 632–636

    Abstract: Neuropathologic confirmation of dementia with Lewy bodies (DLB) involves labeling cytoplasmic Lewy body inclusions for α-synuclein in cortical and subcortical neurons. The authors studied the postmortem brain of a 78-year-old man who had a diagnosis of ... ...

    Abstract Neuropathologic confirmation of dementia with Lewy bodies (DLB) involves labeling cytoplasmic Lewy body inclusions for α-synuclein in cortical and subcortical neurons. The authors studied the postmortem brain of a 78-year-old man who had a diagnosis of DLB by exclusion. The patient had symptoms ascribed to DLB that included fluctuating cognitive changes in attention and executive function with progression to dementia, visual hallucinations, and parkinsonism. Sections from the olfactory bulbs and cortical and subcortical regions were stained with periodic acid-Schiff, as well as immunolabeled with antibodies specific for α-synuclein, tau protein, β-amyloid 1-42, and Chlamydia pneumoniae. Most regions demonstrated mixed neuropathologic features, and α-synuclein was notable in Lewy bodies in the amygdala and hippocampus. Periodic acid-Schiff-positive staining was noted in bodies in the amygdala and olfactory bulbs. In this case of DLB, neuropathologic inclusions were consistent with the disease diagnosis, but also with Alzheimer disease and other neurodegenerative diseases, such as polyglucosan body disease.
    MeSH term(s) Aged ; Autopsy ; Brain/metabolism ; Brain/pathology ; Dementia/pathology ; Humans ; Lewy Body Disease/pathology ; Male ; alpha-Synuclein/metabolism
    Chemical Substances alpha-Synuclein
    Language English
    Publishing date 2019-08-25
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 410350-6
    ISSN 1945-1997 ; 0003-0287 ; 0098-6151
    ISSN (online) 1945-1997
    ISSN 0003-0287 ; 0098-6151
    DOI 10.7556/jaoa.2019.106
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  4. Article ; Online: Etiology and pathogenesis of late-onset Alzheimer's disease.

    Balin, Brian J / Hudson, Alan P

    Current allergy and asthma reports

    2014  Volume 14, Issue 3, Page(s) 417

    Abstract: Alzheimer's disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, ... ...

    Abstract Alzheimer's disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, among other problems, and the late-onset form of the disease is now considered to be the most common cause of dementia among the elderly. While a good deal of research has been focused on elucidating the etiology of the late-onset form for more than two decades, results to date have been modest and have not yet engendered useful therapeutic strategies for cure of the disease. In this review, we discuss the prevalent ideas that have governed this research for several years, and we challenge these ideas with alternative findings suggesting a multifactorial etiology. We review promising newer ideas that may prove effective as therapeutic interventions for late-onset AD, as well as providing reliable means of earlier and more specific diagnosis of the disease process. In the discussions included here, we reference relevant clinical and basic science literature underlying research into disease etiology and pathogenesis, and we highlight current reviews on the various topics addressed.
    MeSH term(s) Age of Onset ; Alzheimer Disease/diagnosis ; Alzheimer Disease/etiology ; Alzheimer Disease/therapy ; Apolipoprotein E4/genetics ; Humans ; Plaque, Amyloid/complications ; Risk Factors
    Chemical Substances Apolipoprotein E4
    Language English
    Publishing date 2014-01-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057370-4
    ISSN 1534-6315 ; 1529-7322
    ISSN (online) 1534-6315
    ISSN 1529-7322
    DOI 10.1007/s11882-013-0417-1
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  5. Article ; Online: Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration.

    Lathe, Richard / Schultek, Nikki M / Balin, Brian J / Ehrlich, Garth D / Auber, Lavinia Alberi / Perry, George / Breitschwerdt, Edward B / Corry, David B / Doty, Richard L / Rissman, Robert A / Nara, Peter L / Itzhaki, Ruth / Eimer, William A / Tanzi, Rudolph E

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2023  Volume 19, Issue 11, Page(s) 5209–5231

    Abstract: Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized ... ...

    Abstract Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.
    MeSH term(s) Humans ; Alzheimer Disease/pathology ; Consensus ; Cognitive Dysfunction/pathology ; Brain/pathology
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.13076
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  6. Article: Role of Microbes in the Development of Alzheimer's Disease: State of the Art - An International Symposium Presented at the 2017 IAGG Congress in San Francisco.

    Fülöp, Tamàs / Itzhaki, Ruth F / Balin, Brian J / Miklossy, Judith / Barron, Annelise E

    Frontiers in genetics

    2018  Volume 9, Page(s) 362

    Abstract: This article reviews research results and ideas presented at a special symposium at the International Association of Gerontology and Geriatrics (IAGG) Congress held in July 2017 in San Francisco. Five researchers presented their results related to ... ...

    Abstract This article reviews research results and ideas presented at a special symposium at the International Association of Gerontology and Geriatrics (IAGG) Congress held in July 2017 in San Francisco. Five researchers presented their results related to infection and Alzheimer's disease (AD). Prof. Itzhaki presented her work on the role of viruses, specifically HSV-1, in the pathogenesis of AD. She maintains that although it is true that most people harbor HSV-1 infection, either latent or active, nonetheless aspects of herpes infection can play a role in the pathogenesis of AD, based on extensive experimental evidence from AD brains and infected cell cultures. Dr. Miklossy presented research on the high prevalence of bacterial infections that correlate with AD, specifically spirochete infections, which have been known for a century to be a significant cause of dementia (e.g., in syphilis). She demonstrated how spirochetes drive senile plaque formation, which are in fact biofilms. Prof. Balin then described the involvement of brain tissue infection by the
    Language English
    Publishing date 2018-09-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2018.00362
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  7. Article ; Online: Chlamydia pneumoniae infection of monocytes in vitro stimulates innate and adaptive immune responses relevant to those in Alzheimer's disease.

    Lim, Charles / Hammond, Christine J / Hingley, Susan T / Balin, Brian J

    Journal of neuroinflammation

    2014  Volume 11, Page(s) 217

    Abstract: Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which infection with Chlamydia pneumoniae (Cpn) has been associated. Cpn is an obligate intracellular respiratory pathogen that may enter the central nervous system (CNS) ...

    Abstract Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which infection with Chlamydia pneumoniae (Cpn) has been associated. Cpn is an obligate intracellular respiratory pathogen that may enter the central nervous system (CNS) following infection and trafficking of monocytes through the blood-brain barrier. Following this entry, these cells may secrete pro-inflammatory cytokines and chemokines that have been identified in the AD brain, which have been thought to contribute to AD neurodegeneration. The objectives of this work were: (i) to determine if Cpn infection influences monocyte gene transcript expression at 48 hours post-infection and (ii) to analyze whether pro-inflammatory cytokines are produced and secreted from these cells over 24 to 120 hours post-infection.
    Methods: Gene transcription was analyzed by RT-PCR using an innate and adaptive immunity microarray with 84 genes organized into 5 functional categories: inflammatory response, host defense against bacteria, antibacterial humoral response, septic shock, and cytokines, chemokines and their receptors. Statistical analysis of the results was performed using the Student's t-test. P-values ≤ 0.05 were considered to be significant. ELISA was performed on supernatants from uninfected and Cpn-infected THP1 monocytes followed by statistical analysis with ANOVA.
    Results: When Cpn-infected THP1 human monocytes were compared to control uninfected monocytes at 48 hours post-infection, 17 genes were found to have a significant 4-fold or greater expression, and no gene expression was found to be down-regulated. Furthermore, cytokine secretion (IL-1β, IL-6, IL-8) appears to be maintained for an extended period of infection.
    Conclusions: Utilizing RT-PCR and ELISA techniques, our data demonstrate that Cpn infection of THP1 human monocytes promotes an innate immune response and suggests a potential role in the initiation of inflammation in sporadic/late-onset Alzheimer's disease.
    MeSH term(s) Adaptive Immunity/immunology ; Alzheimer Disease/immunology ; Alzheimer Disease/microbiology ; Cells, Cultured ; Chlamydia Infections/immunology ; Chlamydophila pneumoniae/immunology ; Chlamydophila pneumoniae/isolation & purification ; Humans ; Immunity, Innate/immunology ; Inflammation/immunology ; Inflammation/microbiology ; Monocytes/immunology ; Monocytes/microbiology
    Language English
    Publishing date 2014-12-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1742-2094
    ISSN (online) 1742-2094
    DOI 10.1186/s12974-014-0217-0
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  8. Article ; Online: Alzheimer disease: the crisis is upon us.

    Simpkins, James W / Wood, Brian E / Balin, Brian J

    The Journal of the American Osteopathic Association

    2010  Volume 110, Issue 9 Suppl 8, Page(s) Sii–2

    MeSH term(s) Alzheimer Disease/epidemiology ; Alzheimer Disease/pathology ; Biomedical Research ; Humans ; Osteopathic Medicine ; Osteopathic Physicians
    Language English
    Publishing date 2010-09
    Publishing country United States
    Document type Introductory Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 410350-6
    ISSN 1945-1997 ; 0003-0287 ; 0098-6151
    ISSN (online) 1945-1997
    ISSN 0003-0287 ; 0098-6151
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  9. Article ; Online: Modern care for patients with Alzheimer disease: rationale for early intervention.

    Galluzzi, Katherine E / Appelt, Denah M / Balin, Brian J

    The Journal of the American Osteopathic Association

    2010  Volume 110, Issue 9 Suppl 8, Page(s) S37–42

    Abstract: More than 5 million people in the United States are afflicted with Alzheimer disease, a condition that is the seventh leading cause of death in the nation. Lacking definitive disease-modifying treatments, modern care for individuals with Alzheimer ... ...

    Abstract More than 5 million people in the United States are afflicted with Alzheimer disease, a condition that is the seventh leading cause of death in the nation. Lacking definitive disease-modifying treatments, modern care for individuals with Alzheimer disease is necessarily multimodal, combining the use of approved pharmaceutic agents (ie, acetylcholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists, antipsychotics), lifestyle and behavioral interventions, and components of palliative care. Some promising experimental treatments are undergoing clinical trials, including immunotherapy to prevent the deposition of β-amyloid, a protein implicated as an etiologic factor in the disease. The authors briefly examine the rationale and methods for screening patients for early indications of the onset of Alzheimer disease. They also describe current and potential treatments for patients with this disease.
    MeSH term(s) Alzheimer Disease/diagnosis ; Alzheimer Disease/drug therapy ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/drug effects ; Cholinesterase Inhibitors/therapeutic use ; Cognition ; Excitatory Amino Acid Antagonists/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Indans/therapeutic use ; Memantine/therapeutic use ; Neuroprotective Agents/therapeutic use ; Phenylcarbamates/therapeutic use ; Piperidines/therapeutic use ; Psychological Tests ; Rivastigmine ; Severity of Illness Index ; Tacrolimus/therapeutic use
    Chemical Substances Amyloid beta-Peptides ; Cholinesterase Inhibitors ; Excitatory Amino Acid Antagonists ; Immunosuppressive Agents ; Indans ; Neuroprotective Agents ; Phenylcarbamates ; Piperidines ; donepezil (8SSC91326P) ; Rivastigmine (PKI06M3IW0) ; Memantine (W8O17SJF3T) ; Tacrolimus (WM0HAQ4WNM)
    Language English
    Publishing date 2010-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 410350-6
    ISSN 1945-1997 ; 0003-0287 ; 0098-6151
    ISSN (online) 1945-1997
    ISSN 0003-0287 ; 0098-6151
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  10. Article ; Online: New thinking on the etiology and pathogenesis of late-onset Alzheimer's disease.

    Hudson, Alan P / Balin, Brian J / Crutcher, Keith / Robinson, Stephen

    International journal of Alzheimer's disease

    2011  Volume 2011, Page(s) 848395

    Language English
    Publishing date 2011-09-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2573333-3
    ISSN 2090-0252 ; 2090-8024
    ISSN (online) 2090-0252
    ISSN 2090-8024
    DOI 10.4061/2011/848395
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