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High Risk of Alzheimer's Seen in Cerebrospinal Fluid Changes

Cerebrospinal fluid

A person’s risk of developing Alzheimer’s disease (AD) within the next decade may be seen in his or her cerebrospinal fluid (CSF), according to a new report in the Archives of General Psychiatry. The authors suggest an estimated 90% of individuals with mild cognitive impairment and specific CSF markers at baseline “will develop AD within 9.2 years.”

CSF reveals high risk of Alzheimer’s disease

One of the classic signs of Alzheimer’s disease is the presence of senile plaques, which consist of aggregated beta-amyloid (Aβ), and neurofibrillary tangles, which contain tau protein. A popular hypothesis concerning Alzheimer’s is that accumulation of the aggregation-prone 42-amino acid isoform of Aβ (Aβ42) in the brain is the force behind the neurodegeneration associated with Alzheimer’s.

Experts believe beta-amyloid begins to gather decades before people experience a decline in their cognitive abilities and that it might be detected by a reduction in cerebrospinal fluid Aβ-42 levels.

The new study was conducted by Peder Buchhave, MD, PhD, of Lund University and Skane University, Sweden, and colleagues, who performed an extended follow-up of 137 patients with mild cognitive impairment who previously had had their CSF levels checked at entry into the study.

In the previous study, the patients were followed-up at a median of 5.2 years, and at that time 57 patients were identified as having Alzheimer’s, 21 had other forms of dementia, and 56 were cognitively stable.

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At the extended follow-up at median of 9.2 years, 72 patients (53.7%) developed Alzheimer’s and 21 (15.7%) had other forms of dementia. Among the patients who developed Alzheimer’s during follow-up, their Aβ42 levels were reduced at baseline and their other biomarkers (tau proteins T-tau and P-tau) were elevated compared with levels in patients who did not develop Alzheimer’s.

The cerebrospinal fluid levels of Aβ42 appeared to be an indicator of patients who would convert early (within 5 years) from mild cognitive impairment to Alzheimer’s disease, because baseline CSF beta-amyloid levels were equally reduced in patients with mild cognitive impairment who developed Alzheimer’s early compared with those who developed the disease later (between 5 and 10 years).

Why this CSF information is important for Alzheimer’s

The authors concluded that “these markers can identify individuals at high risk for future AD at least five to 10 years before conversion to dementia.” But since there are no known treatments that can prevent or cure Alzheimer’s disease, why is early detection important?

Currently, disease-modifying therapies such as immunotherapy, which focuses on promoting or suppressing an immune response from the immune system, has more chance of being successful if it is started in the early stages of the disease. In the meantime, scientists around the world are working on finding effective ways to prevent and treat Alzheimer’s disease and other dementias.

Therefore, being able to identify individuals who are at high risk of developing Alzheimer’s disease by measuring and noting levels of specific cerebrospinal fluid factors can be an important tool in the fight against this devastating disease.

Buchhave P et al. Archives of General Psychiatry 2012; 69(1): 98-106

Picture credit: Wikimedia Commons