Neurology -- Correspondence for Borenstein Graves et al., 57 (8) 1453-1460

Correspondence published:

Head circumference and incident Alzheimer’s disease: Modification by apolipoprotein E: D Gurwitz J Chapman, A Weizman (18 December 2001)

Head circumference and incident Alzheimer’s disease: Modification by apolipoprotein E 18 December 2001

D Gurwitz J Chapman
National Laboratory for the Genetics of Israeli Populations Tel-Aviv Israel,
A Weizman
Send Correspondence to journal:
Re: Head circumference and incident Alzheimer’s disease: Modification by apolipoprotein E

gurwitz{at}post.tau.ac.il D Gurwitz J Chapman, et al.

Borenstein Graves et al. points to an intriguing association between small head circumference and a substantially elevated risk of Alzheimer’s disease (AD) in carriers of the ApoE4 genotype [1]. They conclude that smaller head circumference leads to earlier age at onset of AD, and suggest that this distinctive relationship might reflect a smaller “brain reserve” in such individuals. Consequently, aging-associated neuronal repair mechanisms are more likely to be inadequate in individuals having a smaller head size, resulting in the observed faster AD disease progression.
We would like to propose an alternative explanation for this observation, namely, that smaller head size might be associated with lower CNS availability of insulin or insulin-like growth factor-1 (IGF-1). Small head size at birth was recently found to be strongly associated with lower serum levels of insulin and IGF-1 [2]. Individuals having a smaller head size at birth are likely to have smaller head circumference as adults [3], so that the connection between smaller head size and lower brain insulin/IGF-1 levels assumingly persists through adulthood. Moreover, AD patients were found to have lower CSF insulin compared with healthy adults, an association that was more pronounced in advanced AD [4]. In addition, recent studies have demonstrated that IGF-1 effectively protected neurons against beta amyloid-induced neuronal cell death [5], the major cell-death mechanism believed to underlie AD neuropathology.
Together, these observations might point to a unique connection between reduced CNS insulin or IGF-1 availability and reduced protection against aging-associated neurodegenerative processes culminating in AD, a connection that could be reflected by the newly observed relationship between smaller head size and increased AD risk.
References
1. A. Borenstein Graves, J. A. Mortimer, J. D. Bowen et al. Head circumference and incident Alzheimer’s disease: Modification by apolipoprotein E. Neurology 2001;57:1453-1460.
2. Davidson S, Shtaif B, Gil-Ad I et al. Insulin, insulin-like growth factors-I and -II and insulin-like growth factor binding protein-3 in newborn serum: association with normal fetal head growth and head circumference. J Pediatr Endocrinol Metab. 2001;14:151-158.
3. Barker DJ, Godfrey KM, Osmond C, Bull A. The relation of fetal length, ponderal index and head circumference to blood pressure and the risk of hypertension in adult life. Paediatr Perinat Epidemiol. 1992;6:35- 44.
4. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998;50:164-168.
5. Niikura T, Hashimoto Y, Okamoto T et al. Insulin-like growth factor I (IGF-I) protects cells from apoptosis by Alzheimer's V642I mutant amyloid precursor protein through IGF-I receptor in an IGF-binding protein -sensitive manner. J Neurosci. 2001;21:1902-1910.