This interesting study strengthens the general association of β amyloid pathology with cognitive decline. The study is important since it both illustrates the importance of disturbed β amyloid metabolism in conditions other than Alzheimer disease (AD), and gives clues to the roots of cognitive decline in Parkinson disease (PD).

Cognitive decline in PD was associated with low cerebrospinal fluid (CSF) Aβ1-42 at baseline, but not with total tau or phospho-tau levels. This suggests that brain amyloid pathology contributes to cognitive decline in PD. The findings may be viewed in relation to studies of brain amyloid pathology in normal aging. Brain amyloid accumulation is present in a high proportion of cognitive healthy elderly and in many elderly with stable mild cognitive impairment (1-5). Although this might represent cases of incipient AD, it also suggests individual differences in resistance to amyloid pathology. Concomitant PD pathology might aggravate the toxicity of amyloid, pushing patients over a critical threshold in the amyloid disease cascade. The mechanism behind...  Read more

This interesting study strengthens the general association of β amyloid pathology with cognitive decline. The study is important since it both illustrates the importance of disturbed β amyloid metabolism in conditions other than Alzheimer disease (AD), and gives clues to the roots of cognitive decline in Parkinson disease (PD).

Cognitive decline in PD was associated with low cerebrospinal fluid (CSF) Aβ1-42 at baseline, but not with total tau or phospho-tau levels. This suggests that brain amyloid pathology contributes to cognitive decline in PD. The findings may be viewed in relation to studies of brain amyloid pathology in normal aging. Brain amyloid accumulation is present in a high proportion of cognitive healthy elderly and in many elderly with stable mild cognitive impairment (1-5). Although this might represent cases of incipient AD, it also suggests individual differences in resistance to amyloid pathology. Concomitant PD pathology might aggravate the toxicity of amyloid, pushing patients over a critical threshold in the amyloid disease cascade. The mechanism behind this could be interactions between α-synuclein and amyloid, since these molecules promote each other’s respective accumulation and aggregation (6). In this regard, PD might be a force that drives age-associated subclinical amyloid pathology into clinical symptoms.

To further understand these interesting associations, detailed studies are needed on interactions between α-synuclein and amyloid in vivo in humans. Follow-up investigations of the subjects in the current study would be valuable. Specifically, it would be interesting to know if amyloid pathology at baseline predicted biomarker measurements of neuronal degeneration at follow-up, such as CSF total tau or MRI findings of atrophy.

References:
1. Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, Wilson RS: Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006, 66:1837-1844. Abstract

2. De Meyer G, Shapiro F, Vanderstichele H, Vanmechelen E, Engelborghs S, De Deyn PP, Coart E, Hansson O, Minthon L, Zetterberg H, et al: Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol, 67:949-956. Abstract

3. Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C: Age, neuropathology, and dementia. N Engl J Med 2009, 360:2302-2309. Abstract

4. Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, et al: Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 2009, 65:403-413. Abstract

5. Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, et al: CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009, 302:385-393. Abstract

6. Clinton LK, Blurton-Jones M, Myczek K, Trojanowski JQ, LaFerla FM: Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci, 30:7281-7289. Abstract

View all comments by Niklas Mattsson

Amyloid-β is likely an intermediate in the development of dementia and neuronal cell death in Alzheimer disease and in some cases of Parkinson disease, whereas peroxynitrites may be the principal culprit. Through oxidation and nitration, peroxynitrites disrupt neurotransmissions and lead to a critical shortage of acetylcholine, which is involved in the retrieval of short-term memories. Polyphenols can be used to scavenge peroxynitrites and to partially reverse both peroxynitrite-mediated oxidation and nitration of proteins. The progression of certain types of dementia may thus not only be stopped, but partially reversed.

References:
Chericoni S, Prieto JM, Iacopini P, Cioni P, Morelli I. In Vitro Activity of the Essential Oil Cinnamomum zeylanicum and Eugenol in Peroxynitrite-Induced Oxidative Processes. J of Agri and Food Chem 53(2005):4762-5. Abstract

Ho SC, Tsai TH, Tsai PJ, Lin CC. Protective capacities of certain spices against peroxynitrite-mediated biomolecular damage. Food and Chem Toxicol 46(2008):920-8. Abstract

Marshall KA, Reist M, Jenner P, Halliwell B. The neuronal toxicity of sulfite plus peroxyntrite is enhanced by glutathione depletion: implication for Parkinson's disease. Free Radic Biol Med 27(1999):515-20. Abstract

Smith MA, Richey Harris PL, Sayre LM, Beckham JS, Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease J of Neurosci 17(1997):2653-7. Abstract

View all comments by Lane Simonian