Amyloid-β and α-synuclein cerebrospinal fluid biomarkers and cognition in early Parkinson's disease

Ane Løvli Stav; Dag Aarsland; Krisztina Kunszt Johansen; Erik Hessen; Eirik Auning; Tormod Fladby

doi:10.1016/j.parkreldis.2015.04.027

Amyloid-β and α-synuclein cerebrospinal fluid biomarkers and cognition in early Parkinson's disease

Parkinsonism Relat Disord. 2015 Jul;21(7):758-64. doi: 10.1016/j.parkreldis.2015.04.027. Epub 2015 May 2.

Authors

Ane Løvli Stav¹, Dag Aarsland², Krisztina Kunszt Johansen³, Erik Hessen⁴, Eirik Auning⁵, Tormod Fladby⁶

Affiliations

¹ Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway. Electronic address: aneolo@medisin.uio.no.
² Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway; Alzheimer's Disease Research Centre, Department of Neurobiology, Care Sciences and, Society, Karolinska Institutet, Novum, 141 86 Stockholm, Sweden; Center for Age-Related Diseases, Stavanger University Hospital, 4000 Stavanger, Norway.
³ Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway.
⁴ Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway; Department of Psychology, University of Oslo, Norway.
⁵ Department of Geriatric Psychiatry, Akershus University Hospital, 1478 Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway.
⁶ Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway.

PMID: 25971633
DOI: 10.1016/j.parkreldis.2015.04.027

Abstract

Introduction: Cognitive impairment in early Parkinson's disease (PD) is common and distinct from early Alzheimer's disease. Predictors and mechanisms are only partially known, but α-synuclein, amyloid-β and tau dysmetabolism may be involved. Our aim was to study associations between cerebrospinal fluid biomarkers (CSF) and cognition in non-dementia PD compared to normal controls (NC) and non-PD patients with mild cognitive impairment (MCI non-PD).

Methods: Patients were classified as having normal, subjective or mild cognitive impairment after cognitive screening. CSF levels of total α-synuclein (t-α-syn), amyloid-β (Aβ) 38, 40 and 42, total tau (T-tau) and phosphorylated tau (P-tau) were measured in 34 NC, 31 early, non-dementia PD and 28 MCI non-PD patients. A well validated neuropsychological test battery was administered.

Results: In the PD group, 13 had normal cognition, 4 had subjective and 14 mild cognitive impairment. PD patients had significantly lower CSF biomarker levels of t-α-syn, Aβ38, 40 and 42, T-tau and P-tau compared to NC. Compared to MCI non-PD, t-α-syn, Aβ38 and 40, T-tau and P-tau were also lower, while Aβ42 was significantly higher in the PD group. Aβ38 and 40 correlated strongly with t-α-syn levels in PD. Lower Aβ42 was associated with decreased verbal learning, delayed verbal recall and response inhibition in PD.

Conclusion: While Aβ38, 40 and t-α-syn levels are strongly correlated, only lower Aβ42 was associated with reduced cognitive functions in early PD, mainly connected to medial temporal lobe-based cognitive functions.

Keywords: Alzheimer's disease; Cerebrospinal fluid biomarkers; Cognitive impairment; Parkinson's disease; Pre-dementia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Amyloid beta-Peptides / cerebrospinal fluid*
Biomarkers / cerebrospinal fluid
Cognition / physiology
Cognitive Dysfunction / cerebrospinal fluid*
Cognitive Dysfunction / diagnosis*
Cognitive Dysfunction / psychology
Cross-Sectional Studies
Early Diagnosis
Female
Humans
Longitudinal Studies
Male
Middle Aged
Parkinson Disease / cerebrospinal fluid*
Parkinson Disease / diagnosis*
Parkinson Disease / psychology
Peptide Fragments / cerebrospinal fluid*
alpha-Synuclein / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Biomarkers
Peptide Fragments
alpha-Synuclein
amyloid beta-protein (1-42)