Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration

• Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n = 1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (A beta 42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of A beta 42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, A beta 40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF A beta 42 levels below 530 pg ml(-1). These individuals displayed significantly higher CSF concentrations of t-tau (P < 0.001), p-tau (181) (P < 0.001), neurogranin (P = 0.009) and FABP3 (P = 0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of A beta. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE epsilon 4 and amyloid pathology in healthy older individuals.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

mild cognitive impairment

cerebrospinal-fluid levels

acid-binding

protein

apoe epsilon-4 allele

alzheimers-disease

a-beta

diagnostic-criteria

nondemented individuals

vascular dementia

apolipoprotein-e

Psychiatry

een b

1993

zeitschrift fur gerontologie

v26

p163

lstein mf

1975

journal of psychiatric research

v12

p189

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)