CSF Biomarkers Correlate with Cerebral Blood Flow on SPECT in Healthy Elderly

Abstract

Background: The preclinical patterns of biological markers for Alzheimer’s disease (AD) in vivo need further exploration. The aim of this study was therefore to investigate CSF biomarkers, regional cerebral blood flow (rCBF) and cognitive performance in cognitively healthy older individuals. Method: Within a 2-week period, 32 cognitively healthy older individuals underwent CSF analysis, rCBF measurement and cognitive testing. The CSF was analysed for β-amyloid_1–42 (Aβ42), total tau protein (T-tau) and hyperphosphorylated tau protein (P-tau). The rCBF results were analysed with statistical parametric mapping to investigate rCBF covariance with the other measurements. Results: High CSF P-tau and T-tau levels correlated with decreased rCBF in the right superior posterior medial frontal lobe whereas high CSF P-tau levels also correlated with increased rCBF in the left fronto-temporal border zone area. No significant covariance was seen between rCBF and CSF Aβ42. Neither CSF P-tau and T-tau levels nor rCBF in the current right frontal and left posterior locations were associated with cognitive performance. Conclusions: Our findings suggest a possible correlation between tau pathology and blood flow abnormalities in individuals without any overt cognitive symptoms. An association with AD development is possible but other explanatory mechanisms cannot be excluded.

Altered Amyloid-β and Tau Proteins in Neural-Derived Plasma Exosomes in Patients with Type 2 Diabetes and Orthostatic Hypotension

“…Furthermore, the results of the present study showed thatthe presence of OH in patients with DM was independently associated with elevated T-tau and P-T181-tau levels in neural-derived plasma exosomes. In line with previous studies performed in normal cognition, reductions in cerebral blood ow were associated with increased cerebrospinal uid total tau and phosphorylated tau [28,29]. There are several pathways through which cerebral hypoperfusion may contribute to increased levels of neuronal tau in the brain.…”

Plasma neurofilament light, CSF Aβ, total tau, and p tau 181 is associated with altered cerebral blood flow across Alzheimer’s disease spectrum

“…They found out that the CSF level of p-tau correlated positively with rCBF in the left frontotemporal border zone area. They also realized a negative signi cant correlation between rCBF in the right superior posterior medial frontal lobe in healthy elderly (1). Similarly, our analysis shows a signi cant correlation between the plasma level of NFL and CBF changes in widespread areas of the brain between healthy subjects.…”

“…heretofore most studies emphasized the correlation between CSF level of biomarkers and regional cerebral blood ow changes in neurodegenerative diseases. For example, Stomrud et al investigated the correlation between CSF biomarkers and cerebral blood ow in healthy elderly (1). They found out that the CSF level of p-tau correlated positively with rCBF in the left frontotemporal border zone area.…”

Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

“…Abnormal Aβ downregulation in the pre-AD CSF appears to be associated with the onset of temporoparietal CBF reduction and this hypoperfusion then worsens with the onset of abnormal CSF tau upregulation [12]. High CSF phospho-tau (p-tau) and total tau in the healthy brain have been correlated with reduced CBF in frontotemporal regions [76]. The elucidation of such stereotyped and progressive changes in pre-AD patients and through the course of the disease could aid in differential diagnosis at an early stage of disease progression and aid in preclinical prediction of disease risk, potentially allowing for early intervention.…”