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022 |a 2076-2607 
024 7 |a 10.3390/microorganisms13010090  |2 doi 
035 |a 3159560776 
045 2 |b d20250101  |b d20251231 
084 |a 231538  |2 nlm 
100 1 |a Onisiforou, Anna  |u Translational Neuropharmacology Laboratory, Department of Psychology, University of Cyprus, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus; <email>eleftheria.charalambous@med.uni-greifswald.de</email>; Center of Applied Neuroscience, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus 
245 1 |a Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a For decades, Alzheimer’s Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut–brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut–brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide’s antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions. 
610 4 |a Food & Drug Administration--FDA 
653 |a Neurodegeneration 
653 |a Pathogenesis 
653 |a Alzheimer's disease 
653 |a Probiotics 
653 |a Identification methods 
653 |a Immune system 
653 |a Brain research 
653 |a Herpes simplex 
653 |a Biofilms 
653 |a Accumulation 
653 |a Cytokines 
653 |a Cognition 
653 |a Brain 
653 |a Viral diseases 
653 |a Peptides 
653 |a Animal models 
653 |a Antiviral agents 
653 |a Microbiomes 
653 |a Proteins 
653 |a Microorganisms 
653 |a Hypotheses 
653 |a FDA approval 
653 |a Health risk assessment 
653 |a Microbiota 
653 |a Effectiveness 
653 |a Tumor necrosis factor-TNF 
653 |a Viruses 
653 |a Environmental factors 
653 |a Fecal microflora 
653 |a Infections 
653 |a Vaccines 
653 |a Bacteria 
653 |a Severe acute respiratory syndrome coronavirus 2 
653 |a Pathology 
653 |a Neurodegenerative diseases 
653 |a Herpes zoster 
653 |a Transgenic mice 
653 |a Coronaviruses 
653 |a Intestinal microflora 
653 |a Bacterial infections 
653 |a Antimicrobial agents 
653 |a Viral infections 
653 |a β-Amyloid 
653 |a Senile plaques 
653 |a Respiratory diseases 
653 |a Enzymes 
653 |a Hypothesis testing 
700 1 |a Charalambous, Eleftheria G  |u Translational Neuropharmacology Laboratory, Department of Psychology, University of Cyprus, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus; <email>eleftheria.charalambous@med.uni-greifswald.de</email>; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 1–2, Ellernholzstr., 17489 Greifswald, Germany 
700 1 |a Zanos, Panos  |u Translational Neuropharmacology Laboratory, Department of Psychology, University of Cyprus, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus; <email>eleftheria.charalambous@med.uni-greifswald.de</email>; Center of Applied Neuroscience, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus 
773 0 |t Microorganisms  |g vol. 13, no. 1 (2025), p. 90 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3159560776/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text + Graphics  |u https://www.proquest.com/docview/3159560776/fulltextwithgraphics/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3159560776/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch