Plasma protein profiling for potential biomarkers in the early diagnosis of Alzheimer's disease.

Abstract

OBJECTIVES:

Alzheimer's disease (AD) is the most common cause of dementia in elderly persons. Since the pathology of AD develops slowly from a preclinical or early phase into a fully expressed clinical syndrome, at the time of diagnosis the disease has been progressing for many years. To facilitate the early diagnosis of AD, we performed protein profiling of blood in patients with mild AD as defined by the Functional Assessment Staging (FAST) scale.

METHODS:

Plasma samples from mild AD patients and healthy controls were analyzed using two-dimensional differential gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF/MS) followed by peptide mass fingerprinting.

RESULTS:

Three downregulated proteins were identified: apolipoprotein A-1, alpha-2-HS-glycoprotein, and afamin. Two proteins, including apolipoprotein A-4 and fibrinogen gamma chain, were upregulated in mild AD patients.

DISCUSSION:

Our results suggest that altered expression levels of these proteins in plasma may yield candidate biomarkers for the early diagnosis of AD.

ABBREVIATIONS:

AD, Alzheimer's disease; FAST, Functional Assessment Staging; 2D-DIGE, two-dimensional differential gel electrophoresis; MALDI-TOF/TOF/MS, matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry; CSF, cerebrospinal fluid; Aβ, amyloid beta; MMSE, Mini Mental State Examination; MRI, magnetic resonance imaging; NINCDS-ADRDA, National Institute for Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders Association; CHAPS, 3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate; DTT, dithiothreitol; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; DIA, differential in-gel analysis; BVA, biological variation analysis; CBB, Coomassie brilliant blue; 2DE, two-dimensional gel electrophoresis; TFA, trifluoroacetic acid; ACTH, adrenocorticotropic hormone; Apo A-1, apolipoprotein A-1; AHSG, alpha-2-HS-glycoprotein; Apo A-4, apolipoprotein A-4; MCI, mild cognitive impairment.

• Authors: Yuki Kitamura, Ryoko Usami, Sahoko Ichihara, Hirotaka Kida, Masayuki Satoh, Hidekazu Tomimoto, Mariko Murata, Shinji Oikawa
• Journal: Neurological research (Neurol Res) Vol. 39 Issue 3 Pg. 231-238 (Mar 2017) ISSN: 1743-1328 [Electronic] England
• PMID: 28107809 (Publication Type: Journal Article)

Chemical References

• AFM protein, human
• AHSG protein, human
• Apolipoprotein A-I
• Apolipoproteins A
• Biomarkers
• Blood Proteins
• Carrier Proteins
• Glycoproteins
• P2-C protein, fibrinogen
• Peptide Fragments
• Serum Albumin
• alpha-2-HS-Glycoprotein
• apolipoprotein A-IV
• Fibrinogen
• Serum Albumin, Human

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (blood)
• Apolipoprotein A-I (blood)
• Apolipoproteins A (blood)
• Biomarkers (blood)
• Blood Proteins (analysis)
• Carrier Proteins (blood)
• Early Diagnosis
• Female
• Fibrinogen
• Glycoproteins (blood)
• Humans
• Male
• Middle Aged
• Peptide Fragments (blood)
• Proteomics
• Serum Albumin
• Serum Albumin, Human
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Two-Dimensional Difference Gel Electrophoresis
• alpha-2-HS-Glycoprotein (analysis)