The Viral Hypothesis in Alzheimer’s Disease: Novel Insights and Pathogen-Based Biomarkers

Naughton, Sean X.; Raval, Urdhva; Pasinetti, Giulio Maria

doi:10.3390/jpm10030074

Cited by 15 publications

(14 citation statements)

References 49 publications

(64 reference statements)

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“…Interestingly IL-10 was also increased in SMC and AD, but not in MCI, suggesting that the inflammatory state was not balanced by an anti-inflammatory production [ 159 ]. Considering an eventual infectious origin of the disease [ 160 – 162 ] we have used an extract from Pg, the cornerstone bacteria involved in periodontitis and in AD, in addition to traditional LPS [ 13 , 163 ]. The obtained results were quite similar for both stimuli.…”

Section: Discussionmentioning

confidence: 99%

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Munawara

Catanzaro

et al. 2021

Immun Ageing

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Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.

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Section: Discussionmentioning

confidence: 99%

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Munawara

Catanzaro

et al. 2021

Immun Ageing

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“…Worthy of attention is the fact that a large number of studies have indicated that exposure to various microbial pathogens, viruses, in particular, can accelerate Dementia pathology, suggesting that certain types of infections may play a significant role in Alzheimer's pathogenesis. This is important data because if viral infections increase the risk of AD, the viruses themselves represent a modifiable risk factor that can be treated with the therapeutic intervention [ 40 ].…”

Section: How Does the Sars-cov-2 Virus Affect The Brain?mentioning

confidence: 99%

SARS-CoV-2 Emergency and Long-Term Cognitive Impairment in Older People

Rizzo¹,

Paolisso²

2021

Aging and disease

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The SARS-CoV-2 infection has spread to all continents, affecting particularly older people. The complexity of SARS-CoV2 infection is still under study. Despite respiratory involvement is the main clinical manifestation of COVID-19, neurological manifestations are common. Although it is obvious to give priority to infectious emergency and the infectious disease itself, at present, however, data on potential long-term damages generally and on long-term cognitive functions impairment of older COVID-19 survivors have yet to be investigated. Because the hypothesis on the involvement of SARS-CoV-2 on the long-term cognitive decline pathogenesis would seem difficult to prove, we wanted to explore the brain mechanisms of SARS-CoV-2, in order to provide more in-depth analysis and to draw attention to a topic relevant to basic scientific research and, more generally, to the elderly population.Looking forward, we argue that an early clinical and instrumental cognitive assessment can help prevent and slow down this possible complication or at least improve the quality of life for older people Covid-19 survivor.

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“…Multiple independent laboratories continue to report the detection of viral, bacterial, fungal, protozoal, or other microbially-derived nucleic acid sequences or neurotoxins, such as highly inflammatory bacterial amyloid peptides, lipopolysaccharide (LPS), and many microbe-derived endotoxins within AD affected brain tissues [ 24 , 29 , 34 , 36 , 39 , 40 ]. Microbial biomarkers and systems biology approaches to understand host–microbiome interactions have been suggested by multiple AD researchers that both: ( i ) predict the risk of developing AD well before the onset of cognitive decline; and ( ii ) stimulate and/or accelerate the development of classical AD neuropathology [ 24 , 34 , 39 , 41 , 42 , 43 , 44 ].…”

Section: Novel Emerging and Advanced Diagnostic Biomarkers For Amentioning

confidence: 99%

“…Whether these viral, bacterial, or other microbial DNA- or RNA-based nucleic acids or associated lipoproteins, liposaccharides, peptidoglycans, bacterial-derived amyloids, and/or neurotoxins originate from the gastrointestinal (GI) tract microbiome, a potential brain microbiome, or some dormant pathological microbiome is currently not well understood [ 24 , 35 , 36 , 40 , 43 , 45 ]. Since 1978, at least ~4400 peer-reviewed research articles provide convincing evidence that multiple species of microbes, including viruses, bacteria (especially Gram-negative bacteria), and other microorganisms or their secreted components are strongly associated with the onset and/or the development of AD-type change [ 24 , 29 , 33 , 34 , 41 , 42 , 43 , 46 ]. If microbial presence in the brain is involved in the early initiation or propagation of AD, as currently suspected, then specialized RNA-sequencing applications or nucleic acid-containing gene chips, electrochemical biosensors, or panels of microbial-derived 16S ribosomal RNA (rRNA) interrogated with nucleic acid probes derived from AD biofluids might be useful as novel AD biomarkers in the detection of microbial patterns of expression from human brain tissues at any stage or degree of AD neuropathology.…”

Section: Novel Emerging and Advanced Diagnostic Biomarkers For Amentioning

confidence: 99%

Biomarkers for Alzheimer’s Disease (AD) and the Application of Precision Medicine

Lukiw

Vergallo

Lista

et al. 2020

JPM

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An accurate diagnosis of Alzheimer’s disease (AD) currently stands as one of the most difficult and challenging in all of clinical neurology. AD is typically diagnosed using an integrated knowledge and assessment of multiple biomarkers and interrelated factors. These include the patient’s age, gender and lifestyle, medical and genetic history (both clinical- and family-derived), cognitive, physical, behavioral and geriatric assessment, laboratory examination of multiple AD patient biofluids, especially within the systemic circulation (blood serum) and cerebrospinal fluid (CSF), multiple neuroimaging-modalities of the brain’s limbic system and/or retina, followed up in many cases by post-mortem neuropathological examination to finally corroborate the diagnosis. More often than not, prospective AD cases are accompanied by other progressive, age-related dementing neuropathologies including, predominantly, a neurovascular and/or cardiovascular component, multiple-infarct dementia (MID), frontotemporal dementia (FTD) and/or strokes or ‘mini-strokes’ often integrated with other age-related neurological and non-neurological disorders including cardiovascular disease and cancer. Especially over the last 40 years, enormous research efforts have been undertaken to discover, characterize, and quantify more effectual and reliable biological markers for AD, especially during the pre-clinical or prodromal stages of AD so that pre-emptive therapeutic treatment strategies may be initiated. While a wealth of genetic, neurobiological, neurochemical, neuropathological, neuroimaging and other diagnostic information obtainable for a single AD patient can be immense: (i) it is currently challenging to integrate and formulate a definitive diagnosis for AD from this multifaceted and multidimensional information; and (ii) these data are unfortunately not directly comparable with the etiopathological patterns of other AD patients even when carefully matched for age, gender, familial genetics, and drug history. Four decades of AD research have repeatedly indicated that diagnostic profiles for AD are reflective of an extremely heterogeneous neurological disorder. This commentary will illuminate the heterogeneity of biomarkers for AD, comment on emerging investigative approaches and discuss why ‘precision medicine’ is emerging as our best paradigm yet for the most accurate and definitive prediction, diagnosis, and prognosis of this insidious and lethal brain disorder.

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The Viral Hypothesis in Alzheimer’s Disease: Novel Insights and Pathogen-Based Biomarkers

Cited by 15 publications

References 49 publications

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

SARS-CoV-2 Emergency and Long-Term Cognitive Impairment in Older People

Biomarkers for Alzheimer’s Disease (AD) and the Application of Precision Medicine

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