Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections

Abstract

The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.

Diagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer's disease

“…Other causes of isolated low CSF A β 42 are also possible, including increased peptide degradation, altered transport over the blood–brain barrier, and differences in the species of A β measured by PET versus ELISA or other immunoassays, although it is not known if this is important for the development of AD. Diseases that are associated with low CSF A β 42 in the absence of A β plaque pathology include cerebrovascular disease, and neuroinflammatory and neuroinfectious conditions such as bacterial meningitis, HIV-associated dementia, and multiple sclerosis 27,28. In these conditions, C-terminally truncated CSF A β peptides (e.g., A β 38 and A β 40) are also reduced, which is not the case in AD, and a ratio between CSF A β 42 to A β 40 may help to resolve this issue.…”

Role of HIV in Amyloid Metabolism

“…Three studies have found reductions in CSF Aβ42 in HAND individuals (Clifford et al 2009a; Krut et al 2013), or HIV+ patients with CNS co-infections (Gisslén et al 2009). More recently, a study has shown an increase in CSF Aβ42 with early HIV infection compared to HIV− controls (Peluso et al 2013).…”

Cerebrospinal fluid tau proteins in status epilepticus

“…High total-tau (ttau) and phosphorylated-tau (p-tau) CSF levels are considered to index both axonal and neuronal damage and are currently used in clinical research for early Alzheimer's disease diagnosis together with the determination of amyloid precursor protein cleavage peptides such as Abeta 1-42 (Aβ 1-42 ) [14,15]. Increased levels of CSF tau proteins are also found in patients with various neurological diseases, such as traumatic brain injury, acute ischemic stroke, viral encephalitis, and Creutzfeldt-Jacob disease, suggesting that tau CSF levels reflect the extent of axonal damage and neuronal degeneration [16][17][18][19][20].…”