Elsevier

Neurobiology of Aging

Volume 30, Issue 12, December 2009, Pages 1895-1901
Neurobiology of Aging

CSF biomarker levels in early and late onset Alzheimer's disease

https://doi.org/10.1016/j.neurobiolaging.2008.02.007Get rights and content

Abstract

Objective

To compare CSF levels of beta-amyloid 1–42 (Aβ1–42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) between AD patients and controls according to age.

Methods

248 AD patients (48% men) and 127 controls (51% men, 22 volunteers and 105 subjective complainers) underwent lumbar puncture. Both patients and controls were divided into a young (<65 years) and old (≥65 years) group.

Results

All three biomarkers showed main effects of diagnosis (p < 0.001). There was an interaction between diagnosis and age for all three biomarkers (p < 0.05), as old controls had lower Aβ1–42 and higher (p)tau than young controls (Aβ1–42 699 ± 250 versus 866 ± 191 pg/ml, tau 408 ± 245 versus 243 ± 102 pg/ml, ptau-181 60 ± 28 versus 42 ± 15 pg/ml), but there was no difference according to age among AD patients (Aβ1–42 451 ± 178 versus 425 ± 146 pg/ml, tau 741 ± 460 versus 798 ± 467 pg/ml, ptau-181 91 ± 42 versus 91 ± 41 pg/ml).

Conclusion

We found that the older control group had lower Aβ1–42 and higher (p)tau compared to the younger control group. This suggests that older individuals may have AD pathology, even in the absence of objective cognitive impairment.

Introduction

Alzheimer's disease (AD) is the most common form of dementia. The neuropathological hallmarks of AD are neuritic plaques, mainly composed of beta-amyloid 1–42 (Aβ1–42), and neurofibrillary tangles containing (phosphorylated) tau. There is evidence that CSF levels of Aβ1–42 and tau reflect the presence of the neuropathological hallmarks of AD from neuropathological and PIB-PET studies (Clark et al., 2003, Fagan et al., 2006, Strozyk et al., 2003). In addition, CSF levels of Aβ1–42 and (phosphorylated) tau have been shown to discriminate AD from controls with reasonable accuracy, although biomarker levels do overlap between groups (Blennow and Hampel, 2003, Schoonenboom et al., 2004).

The term AD was originally reserved for individuals with presenile onset of symptoms, whereas the expression senile dementia was used when onset was after 65 years of age (Roth, 1955). Later in history these disorders were held to represent a single, homogeneous entity, as it was observed that plaques and tangles are present in the brains of patients with both early and late onset AD (Tomlinson et al., 1970). However, post mortem studies have shown that in young patients with AD there is a strong correlation between dementia severity and plaque and tangle burden, whereas this association is not found in elderly patients (Prohovnik et al., 2006). Furthermore, plaque and tangle load as well as the cholinergic deficits may be more severe in young than in old AD patients (Hansen et al., 1988, Wilcock and Esiri, 1982). Therefore, one would expect differences in CSF biomarker levels for young and old AD patients.

Few studies have analysed differences in CSF biomarker levels in patients with early versus late onset AD and came up with inconsistent results (Andreasen et al., 1999, Green et al., 1999, Iqbal et al., 2005, Rosler et al., 1996, Sjogren et al., 2000). The aim of this study was to compare CSF levels of Aβ1–42, total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) between AD and controls according to age with the ultimate goal to gain further insight in possible differences of AD pathology in young and old patients.

Section snippets

Study population

248 patients with Alzheimer's disease and 127 control subjects (22 volunteers without cognitive complaints and 105 patients with subjective complaints) underwent lumbar puncture (LP) at the Alzheimer Center of the VU University Medical Center (VUMC) between November 2000 and December 2006. All patients underwent a standardized clinical assessment, including medical history, physical and neurological examination including Mini Mental State Examination (MMSE) (Folstein et al., 1975) laboratory

Results

Demographic characteristics are represented in Table 1. No differences were found for sex between young and old AD patients and controls. Age showed no differences in the old group, but in the young group patients were slightly older than controls (p < 0.01). Of the 55 controls with clinical follow-up, six showed clinical progression (4 mild cognitive impairment (MCI) (one young, three old controls), one AD and one frontotemporal lobar degeneration (both young controls)). Young and old controls

Discussion

We found that the difference in CSF biomarker levels between young AD patients and controls is larger than the difference between old AD patients and controls. As CSF biomarker levels between young and old AD patients were similar, this was attributable to the old control group having lower Aβ1–42 and higher (p)tau compared to the young control group.

Few previous studies compared CSF biomarker levels in young and old AD patients. One study found lower Aβ1–42 levels in old AD patients, another

Disclosure

All authors report that there are no actual or potential conflicts of interest that could inappropriately influence their work, including any financial, personal or other relationships with other people or organizations within three years of beginning the work submitted. There was no additional funding.

Acknowledgement

The Alzheimer Center VUMC is supported by Alzheimer Nederland and Stichting VUMC fonds.

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