Increased Levels of Truncated Nerve Growth Factor Receptor in Urine of Mildly Demented Patients With Alzheimer's Disease

Lindner, Mark D.; Gordon, Deidre D.; Miller, Judith M.; Tariot, Pierre N.; McDaniel, Keith D.; Hamill, Robert W.; DiStefano, Peter S.; Loy, Rebekah

doi:10.1001/archneur.1993.00540100049013

Cited by 21 publications

(13 citation statements)

References 38 publications

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“…In line with this hypothesis, a transient increase in LNGFR was observed at the beginning of ChAT/LNGFR-positive degeneration in AD (Lindner et al 1993) and during the initial period of deterioration of spatial learning and memory functions in aged rats (Lindner et al 1994). The finding of supranormal LNGFR levels could be of interest in the light of recent experiments demonstrating that unbound LNGFRs can induce apoptotic neuronal death (Rabizadeh et al 1993) and that LNGFR expression can enhance β-amyloid peptide toxicity (Rabizadeh et al 1994).…”

Section: Discussionmentioning

confidence: 72%

Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits

et al. 1997

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Quantitative in situ hybridization was used to examine the expression of mRNA for nerve growth factor (NGF) and its receptors, p140Trk (TrkA) and p75LNGFR (LNGFR), in different brain regions of adult (3-month-old) and aged (27-month-old) Wistar rats. The brain regions studied were hippocampus (dentate gyrus, CA3 region), basal forebrain (medial septum, diagonal band) and caudate-putamen. Prior to hybridization histochemistry behaviorally impaired as well as severely impaired animals were selected from a large group of old rats according to their performance in the Morris water maze. The impaired rats showed longer escape latencies and, thus, implicitly impaired performance in the place version of the task, but did not differ from adult controls on the platform crossing measure registered during the spatial probe trial. The severely impaired rats were significantly impaired on both measures, both in comparison with the adult animals and in comparison with the impaired aged rats. Inspection of the hippocampus revealed no age- or performance-related changes in NGF mRNA levels. The overall expression of TrkA mRNA in basal forebrain and caudate was found to be decreased in the impaired (-20%) as well as the severely impaired aged rats (-17%). A significant increase in p75LNGFR mRNA was found in the basal forebrain of the impaired rats in comparison with the severely impaired aged rats (+35%) and adult animals (+33%). These findings show that age-related maze performance deficits are accompanied by a decrease in basal forebrain and striatal TrkA mRNA expression. The increase in basal forebrain LNGFR mRNA levels observed in impaired, but not severely impaired, aged rats may reflect an early manifestation of processes underlying age-related cognitive deficits and may constitute a restorative and/or compensatory mechanism, since these rats displayed fewer deficits in navigation of the maze.

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Section: Discussionmentioning

confidence: 72%

Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits

et al. 1997

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“…They reported ∼2.0 µg of p75NTR ECD /ml urine for mildly demented people and 1.1 µg of p75NTR ECD /ml urine healthy controls [41] indicating p75NTR ECD comprises ∼5.0% of normal urinary protein. In comparison, we show 0.0075 µg p75NTR ECD /ml urine and 0.002 µg p75NTR ECD /ml urine for ALS patients and healthy controls, respectively.…”

Section: Discussionmentioning

confidence: 99%

The Extracellular Domain of Neurotrophin Receptor p75 as a Candidate Biomarker for Amyotrophic Lateral Sclerosis

et al. 2014

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Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1G93A mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (p<0.001) than 12 controls (2.6±0.2 ng/mg creatinine) and 19 patients with other neurological disease (Parkinson's disease and Multiple Sclerosis; 4.1±0.2 ng/mg creatinine). Pilot data of disease progression rates in 14 MND patients indicates that p75NTRECD levels were significantly higher (p = 0.0041) in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1G93A mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

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“…Increased serum NGF levels might reduce the excitatory threshold of bladder to dorsal root ganglia, resulting in increased mechanosensitivity of the bladder wall. Increased uNGF‐Rt levels have also been found in patients with mild Alzheimer’s disease [26]. It seems rational to hypothesise that stroke patients with moderate to severe neurological impairment have increased circulating NGF and this causes an increase in uNGF level, while those with mild neurological impairment might have smaller increases in circulating NGF levels associated with minimal or undetectable increases in uNGF levels.…”

Section: Discussionmentioning

confidence: 99%

Urinary nerve growth factor level is correlated with the severity of neurological impairment in patients with cerebrovascular accident

Liu

Chancellor

et al. 2009

BJU International

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normalized to the concentration of urinary creatinine (uNGF/Cr). RESULTSThe median (interquartile range) uNGF/Cr levels were significantly higher in patients, at 0.13 (0-1.04), than in normal subjects (undetectable). The uNGF/Cr levels correlated well with the severity of neurological impairment. Patients with none/minimal neurological impairment had no detectable uNGF/Cr level, like the controls. Patients with mild/moderate impairment had levels of 0.27 (0.09-0.8) and with severe impairment level of 1.53 (0.5-3.0) (both P < 0.001), significantly greater than that of none/ minimal impairment or controls. However, uNGF/Cr levels were not correlated with age, location of CVA, multiplicity of CVA, duration of CVA, urodynamic findings or the presence of urge urinary incontinence. CONCLUSIONSThe uNGF level is correlated with the severity of neurological impairment in patients with CVA but not with urge symptoms or urodynamic findings, suggesting elevated uNGF might be a result of the neurological lesion rather than lower urinary tract dysfunction in CVA.

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Increased Levels of Truncated Nerve Growth Factor Receptor in Urine of Mildly Demented Patients With Alzheimer's Disease

Cited by 21 publications

References 38 publications

Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits

Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits

The Extracellular Domain of Neurotrophin Receptor p75 as a Candidate Biomarker for Amyotrophic Lateral Sclerosis

Urinary nerve growth factor level is correlated with the severity of neurological impairment in patients with cerebrovascular accident

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