Cerebrospinal fluid biomarkers for pathological processes in Alzheimer's disease

Abstract

The CSF biomarkers total tau, phosphorylated-tau and the 42 amino acid isoform of amyloid beta reflect core elements of AD, that is, axonal degeneration, tangle disease and senile plaques, have been thoroughly tested and provide high diagnostic accuracy in the discrimination of patients with AD as compared with cognitively normal controls. They are also highly predictive of AD with dementia in patients with mild cognitive impairment, and have been included in new diagnostic criteria. New biomarkers may add to their diagnostic performance. Other potential fields of use include the monitoring of disease progression or pharmacodynamic drug effects. A common denominator for the candidate biomarkers is the need for validation in further studies to clarify their potential.

Toward more predictive genetic mouse models of Alzheimer's disease

“…Indeed, the most stable and commonly used biomarkers used in human patients today are CSF measurements of Aβ42/Aβ40 and p-Tau/t-Tau; these have been reviewed previously ([34, 35]. However, additional pathologies may be critical in the development of AD and include neuroinflammation, neurogenesis disruption, and vascular dysfunction that should be considered in the phenotypic assessment of AD models.…”

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].…”

A multivariate predictive modeling approach reveals a novel CSF peptide signature for both Alzheimer's Disease state classification and for predicting future disease progression

“…Furthermore, elevated levels of t-tau and p-tau have also been observed in MCI patients that developed AD compared to stable MCI patients and normal controls [8,9]. Given the possibility that a variety of other pathological processes may be simultaneously ongoing in the AD brain (e.g., oxidative stress, inflammation and synaptic dysfunction), apart from these three core CSF biomarkers, other biomarkers could reflect pathogenesis of AD and reveal new biomarkers for AD [10]. …”