A rapid and sensitive fluorescence method for detecting urine formaldehyde in patients with Alzheimer’s disease

Abstract

Background Morning urine formaldehyde concentrations could predict the severe degree of dementia in patients with post-stroke dementia and Alzheimer’s disease. However, the routinely available technique of high-performance liquid chromatography (HPLC) for detecting urine formaldehyde requires expensive and sophisticated equipment. Methods We established a fluorescence spectrophotometric method by using a formaldehyde-specific fluorescent probe-NaFA (λex/em = 430/543 nm). As a standard reference method, the same batch of urine samples was analysed by HPLC with a fluorescence detector (λex/em = 346/422 nm). Then we compared the limits of detection and the limits of quantization detected by these two methods and addressed the relationship between urine formaldehyde and human cognitive ability. The Mini-Mental State Examination (MMSE), Clinical Dementia Rating and Activities of Daily Living scale were used to evaluate cognition function in 30 Alzheimer’s disease patients and 52 healthy age-matched controls. Results Limits of detection and limits of quantization (1.27 and 2.48 μM) of the NaFA probe method were more accurate than Fluo-HPLC (1.52 and 2.91 μM). There was no difference in the detected formaldehyde values within day and day-to-day. Notably, only 3/82 urine formaldehyde concentrations detected by NaFA probe were below zero, while 12/82 of the values analysed by Fluo-HPLC were abnormal. More importantly, there were negatively correlated between urine formaldehyde concentrations detected by NaFA probe and MMSE scores, but positively correlated with Clinical Dementia Rating scores in Alzheimer’s disease patients. Conclusions This detecting urine formaldehyde method by NaFA probe was more rapid, sensitive and accurate than Fluo-HPLC.

Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading

“…To elucidate the relationship between cerebellar formaldehyde levels and motion functions under weightless conditions, we first made a mouse model of HU stress by subjecting the hind limbs to unloading for 2 consecutive weeks as described previously 10 , 19 , 20 , and then examined the formaldehyde concentrations in the brain and assessed motor behaviors. Using an in vivo small animal imaging system with the free formaldehyde fluorescence probe NaFA ( λ ex/em = 440/550 nm) 21 , 22 (Fig. 1a ), we found that HU-stress induced a time-dependent elevation in the fluorescence intensity due to cerebellar formaldehyde (values on day 7 vs. day 0: n = 6, t = 7.827, df = 10, p < 0.001; values on day 14 vs. day 0: n = 6, t = 11.43, df = 10, p < 0.001; one-way ANOVA).…”

“…3 b, c ), which was detected by a mitochondrial formaldehyde-sensitive fluorescence probe ( λ ex/em = 440/550 nm) 29 and a Ca 2+ -sensitive probe Fura-2 AM, respectively 30 . Meanwhile, we observed the effects of microgravity on cytoplasmic formaldehyde as quantified by a free formaldehyde fluorescence probe 22 . Our results indicated that the cultured neuronal cells exhibited marked elevations in the levels of intracellular Ca 2+ ( n = 18, t = 5.027, df = 34, p < 0.0001; unpaired t -test) (Fig.…”

“…The cerebellar formaldehyde levels were quantified using an in vivo small animal imaging system with an NaFA probe 22 and Fluo-HPLC 23 , respectively. We found that the formaldehyde fluorescence intensity in FDH −/− mice was elevated 3-fold compared to that in control mice ( n = 6, t = 17.82, df = 10, p < 0.0001; unpaired t -test) (Fig.…”

Novel Method of Analysis for the Determination of Residual Formaldehyde by High-Performance Liquid Chromatography

“…Fluorescence derivatisation methods [ 20 – 23 ] are based upon reactions forming compounds possessing fluorescence properties. These include reaction of aldehydes with β -diketones (Hantzsch reaction), such as 2,4-pentanedione [ 34 ] and 1,3-cyclohexanedione [ 35 ], Fluoral-P [ 36 – 39 ], anthrone [ 40 ], m-aminophenol [ 41 ], and ampicillin [ 21 ], with the latter showing lack of selectivity [ 42 ].…”

Low and High Molecular Weight FGF-2 Have Differential Effects on Astrocyte Proliferation, but Are Both Protective Against Aβ-Induced Cytotoxicity

“…Alzheimer's disease (AD) is the most prevalent type of dementia and is characterized by the progressive decline, and ultimately, loss of multiple cognitive functions (Ai et al, 2019;Das et al, 2019). The characteristic pathologic hallmarks, including neuritic plaques, synaptic loss (Katsouri et al, 2015), neurofibrillary tangles, and deposits of Aβ have been observed in the brain of AD patients (Granadillo et al, 2017).…”