Neurofilament proteins NF-L, NF-M and NF-H in brain of patients with Down syndrome and Alzheimer's disease

Neurofilaments (NFs) are integral constituents of the neuron playing a major role in brain development, maintenance, regeneration and the pattern of expression for NFs suggests their contribution to plasticity of the neuronal cytoskeleton and creating and maintaining neuronal architecture. Using immune-histochemical techniques the altered expression of NFs in Down syndrome (DS) and Alzheimer's disease (AD) has been already published but as no corresponding systematic immune-chemical study has been reported yet, we decided to determine proteins levels of three NFs in several brain regions of DS and AD brain. We evaluated immunoreactive NF-H, NF-M and NF-L levels using Western blotting in brain regions temporal, occipital cortex and thalamus of patients with DS (n = 9), AD (n = 9) and controls (n = 12). We found significantly increased NF-H in temporal cortex (controls: means 0.74 +/- 0.39 SD; DS: means 3.01 +/- 2.18 SD) of DS patients and a significant decrease of NF-L in occipital cortex of DS and AD patients (controls: means 1.19 +/- 0.86 SD; DS: means 0.35 +/- 0.20; AD: 0.20 +/- 0.11 SD). We propose that the increase of NF-H in temporal cortex of DS brain is due to neuritic sprouting as observed in immune-histochemical studies. The increase may not be caused by the known accumulation of NFs in plaques, tangles or Lewy bodies due to our solubilization protocol. The decrease of NF-L in occipital cortex of DS and AD patients may well be reflecting neuronal loss. Altogether, however, we suggest that NFs are not reliable markers for neuronal death, a hallmark of both neurodegenerative diseases, in DS or AD. The increase of NF-H in DS or the decrease of NF-L in DS and AD leaves the other NFs unchanged, which points to dysregulation in DS and AD and raises the question of impaired structural assembly of neurofilaments.