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Novel Blood Biomarker For The Early Detection Of Frontotemporal Dementia: “CSF Placental Growth Factor”

Author: Medical Team

Medical Blog

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Background

The World Health Organization (WHO) estimates that there are 47.5 million dementia sufferers worldwide and that 7.7 million new cases are diagnosed each year. Frontotemporal dementia (FTD) disorders are responsible for 25% of dementia cases in people older than 65 years old, making them the second most common cause of dementia in patients under the age of 65 years.

Recent a study was published in “Annals of Clinical and Translational Neurology”, highlighting the role of different blood biomarkers in the early detection of FTD. Diagnosis of FTD is challenging due to the symptomatic overlap, neurodegeneration, heterogeneity of clinical presentation with other neurodegenerative diseases. PlGF, a novel blood biomarker is identified in the early detection of FTD

The early identification of FTD can be aided by particular blood biomarkers and neuroimaging, which are proving to be crucial biomarker clues. A growing body of research shows that Placental Growth Factor (PlGF) has biological impacts on pathological inflammation and angiogenesis linked to hematologic disorders, ischemia and cancer, in addition to its regulatory role during pregnancy. For the early identification of FTD, modulation of PlGF is also required in diseases associated with the central nervous system.

About Placental Growth Factor (PlGF)

Frontotemporal dementia (FTD) is one of the most common early-onset dementia with a reported prevalence rate of 3–26% in demented people with disease onset before 65 years of age.

A vascular endothelial growth factor (VEGF) family member, PlGF was first identified in the placenta but was later discovered to be expressed in other tissues. Elevated cerebrospinal fluid (CSF) levels of PlGF in Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with lewy bodies (DLB) has been investigated.

About the Study

At the Memory Clinic of Skane University Hospital in Malmo, Sweden, 75 patients with Alzheimer's disease (AD), 47 patients with Dementia with Lewy Bodies and Parkinson Disease (DLB-PDD), 33 patients with vascular dementia (VaD), 27 patients with FTD, and 50 healthy controls were enrolled in the cohort study.

In this cohort study, 96 people (recruited from the same clinic) had a baseline diagnosis of mild cognitive impairment (MCI). 34 of those had converted to AD (MCI-AD) after an average clinical follow-up duration of 5.7 years (3.0-9.6), whereas 62 had retained cognitive stability (sMCI). Medical professionals with considerable experience in cognitive problems evaluated each trial participant.

Higher accuracies for PlGF were found in a sub-cohort analysis (n=267) that compared the diagnostic performance of PlGF alone, with tau, and with tau and amyloid-beta 42 to neurofilament light chain. In all the subjects CSF levels of PlGF were analysed.

CSF sampling and biological assays

CSF samples were taken from all patient groups and control groups that weren't fasting. To prevent gradient effects, CSF was collected in polypropylene tubes and carefully mixed. To remove cells and debris, all samples were centrifuged within 30 minutes at +4°C at 2000g for 10 min. In anticipation of biochemical examination, samples were kept in aliquots at 80°C. Using electrochemiluminescence immunoassay, CSF PLGF was quantified.

 

 

Control

(n = 50)

sMCI

(n = 62)

MCI – AD

(n = 34)

AD

(n = 75)

DLB – PDD

(n = 47)

VaD

(n = 33)

FTD

(n = 27)

Age

74.2

69.2

74.9

76.4

74.5

75.9

70.1

Sex, (% Female)

72%

56%

65%

68%

40%

46%

44%

Apolipoprotein E (APOE)

27%

47%

82%

65%

54%

25%

27%

Mini‐Mental State Examination (MMSE)

29.0

28.2

26.4

19.5

21.9

21.7

22.8

Aβ42, pg/ml

695

486

317

260

340

396

709

Aβ40, pg/ml

5206

3821

4232

3899

3170

3238

4509

tau, pg/ml

443

437

645

766

472

441

385

PlGF, pg/ml

54.8

64.1

70.5

79.5

89.5

94.2

166.7

Table 1.1 CSF levels of PlGF in Diagnostic Groups

 

Conclusion

The findings imply that PlGF presents a very promising biomarker for the early identification of FTD. Individuals with FTD have concentrations that are 1.8–2.1 times greater than those of people with AD, DLB–PDD, and VaD. By separating FTD from both controls and sMCI, PlGF alone displayed extremely high accuracies, sensitivities, and specificities.

Reference

  1. Hansson, O., Santillo, A. F., Meeter, L. H., Nilsson, K., Landqvist Waldö, M., Nilsson, C., Blennow, K., van Swieten, J. C., & Janelidze, S. (2019). CSF placental growth factor - a novel candidate biomarker of frontotemporal dementia. Annals of clinical and translational neurology6(5), 863–872. https://doi.org/10.1002/acn3.763
  2. Young JJ, Lavakumar M, Tampi D, Balachandran S, Tampi RR. Frontotemporal dementia: latest evidence and clinical implications. Therapeutic Advances in Psychopharmacology. 2018;8(1):33-48. doi:10.1177/2045125317739818

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