TABLE 1.

Overview of infections associated with neurodegenerative diseases.

Disease	Pathogen	Type of pathogen	Association with disease processes
Alzheimer’s disease (AD)	Chlamydia pneumoniae	Gram-negative bacteria	• Detected in post-mortem brains and brain tissue samples of AD patients (Balin et al., 1998; Gérard et al., 2006) • Upregulated β and γ secretase in infected astrocytes, promoted Aβ peptide formation in vitro(Al-Atrache et al., 2019)
	Porphyromonas gingivalis	Gram-negative bacteria	• Detected in the brains and biofluids of AD patients (Poole et al., 2013; Dominy et al., 2019) • Increased production of TNF-α, IL-6, and IL-1β in mice (Ding et al., 2018; PMID: Ilievski et al., 2018) • Increased Aβ peptide accumulation in the brain of infected or PgLPS-treated mice (Wu et al., 2017; Ilievski et al., 2018)
	Salmonella typhimurium	Gram-negative bacteria	• Increased Aβ peptide deposition in the brain of infected mice to bind and entrap bacteria (Kumar et al., 2016)
	Human herpesvirus 6A (HHV-6A) and 7 (HHV-7)	Herpesvirus	• Identified HHV-6 and HHV-7 in late-onset AD patients (Readhead et al., 2018) • Reduced autophagy, promoted accumulation of hyperphosphorylated Tau and Aβ peptides (Romeo et al., 2020) • Infected microglia enhanced Aβ peptide deposition and Tau phosphorylation (Bortolotti et al., 2019)
	Herpes simplex virus 1 (HSV-1)	Herpesvirus	• Found HSV-1 antibodies in female AD patients over 60 years of age (Lövheim et al., 2015a) • Detected HSV-1 DNA in the brains of AD patients (Wozniak et al., 2009b) • Increased β-amyloidosis as an antimicrobial defense mechanism, which increased senile plaque formation (Eimer et al., 2018) • Promoted Tau hyperphosphorylation and damage in primary neurons (Zambrano et al., 2008)
	Human immunodeficiency virus (HIV-1)	Retrovirus	• Inhibited Aβ degradation in human brain cultures (Rempel and Pulliam, 2005) • Promoted cleavage of APP into Aβ peptides (Kim et al., 2013; Hategan et al., 2017) • Promoted Tau hyperphosphorylation and NFT deposition (Giunta et al., 2009). • Enhanced pro-inflammatory cytokine secretion from microglia, astrocytes, and monocytes (Nookala and Kumar, 2014; Haij et al., 2015; Liu and Kumar, 2015) • Activated immune signaling pathways (Herbein and Khan, 2008; Herbein, 2016) • Promoted Aβ secretion from primary hippocampal neurons (Aksenov et al., 2010) • Inhibited apoptosis in infected human neuroblastoma cells (Thomas et al., 2009) • Increased trafficking of Aβ to neural progenitor cells (András et al., 2017, 2020) • Detected elevated hyperphosphorylated Tau in the hippocampus of HIV-infected patients (Anthony et al., 2006)
	Human T cell leukemia virus type I (HTLV-1)	Retrovirus	• Increased activation of Tau kinases, increased Tau phosphorylation in vitro (Maldonado et al., 2011)
Parkinson’s disease (PD)	Helicobacter pylori	Gram-negative bacteria	• Found in PD patients in high prevalence (Huang et al., 2018; McGee et al., 2018) • Improved motor functions in patients who have cleared H. pylori infection (Lahner et al., 2009; Huang et al., 2018)
	Hepatitis C virus (HCV)	Flavivirus	• Increased neuronal death (Weissenborn et al., 2006; Abushouk et al., 2017; Wijarnpreecha et al., 2018) • Increased production of pro-inflammatory cytokines and chemokines from activated microglia (Lyons and Benveniste, 1998; Wu et al., 2015; Abushouk et al., 2017)
	Human immunodeficiency virus (HIV-1)	Retrovirus	• Infected dopaminergic neurons and associated with development of dementia (Nath et al., 2000)
	Cytomegalovirus (CMV)	Herpesvirus	• Elevated levels of circulating pro-inflammatory myeloid cells found in PD patients (Goldeck et al., 2016)
	Theiler’s murine encephalomyelitis virus (TMEV)	Picornavirus	• Infected dopaminergic neurons in vivoand promoted neurodegeneration (Oliver et al., 1997)
	Japanese Encephalitis virus (JEV)	Flavivirus	• Infected dopaminergic neurons, modulated dopamine signaling, promoted neurodegeneration (Simanjuntak et al., 2017)
	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	Coronavirus	• Detected viral RNA and evidence of microglia activation and T lymphocyte infiltration in the post-mortem brain of COVID-19 patients (Matschke et al., 2020)
Amyotrophic lateral sclerosis (ALS)	Human immunodeficiency virus (HIV-1)	Retrovirus	• Reduced glutamate transport and increased neuronal excitotoxicity in infected human astrocytes in vitro (Wang et al., 2003) • Increased production and mislocalization of Fus in iPSC-derived spinal neurons (Bellmann et al., 2019) • Promoted axonal degeneration (Berth et al., 2016)
	Human endogenous retrovirus K (HERV-K)	Retrovirus	• Regulated activation of TDP-43 (Li et al., 2015)
	Theiler’s murine encephalomyelitis virus (TMEV)	Picornavirus	• Promoted TDP-43 phosphorylation, mislocalization, and aggregation following infection in vitroandin vivo(Masaki et al., 2019)
	Rabies virus (RABV)	Rhabdovirus	• Increased production and mislocalization of Fus in iPSC-derived spinal neurons (Bellmann et al., 2019)