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What’s Behind the Decline? The Role of White Matter in Brain Aging

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Abstract

The specific molecular events that underlie the age-related loss of cognitive function are poorly understood. Although not experimentally substantiated, age-dependent neuronal loss has long been considered central to age-related cognitive decline. More recently, age-related changes in brain white matter have taken precedence in explaining the steady decline in cognitive domains seen in non-diseased elderly. Characteristic alterations in the ultrastructure of myelin coupled with evidence of inflammatory processes present in the white matter of several different species suggest that specific molecular events within brain white matter may better explain observed pathological changes and cognitive deficits. This review focuses on recent evidence highlighting the importance of white matter in deciphering the course of “normal” brain aging.

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Abbreviations

ARCD:

Age-related cognitive decline

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

MRI:

Magnetic resonance imaging

FA:

Fractional anisotropy

R 2 :

Transverse relaxation rates

CNS:

Central nervous system

NFT:

Neurofibrillary tangle

iNOS:

Inducible nitric oxide synthase

MHC:

Major histocompatibility complex

CAOs:

Complement activated oligodendrocytes

C3aR:

Complement C3a receptor

PNS:

Peripheral nervous system

GFAP:

Glial acidic fibrillary protein

ACT:

α1-Antichymotrypsin

MBP:

Myelin basic protein

PLP:

Proteolipid protein

MAG:

Myelin-associated glycoprotein

CNP:

2’,3’ Cyclic nucleotide phosphodiesterase

MOSP:

Myelin oligodendrocyte specific protein

EAE:

Experimental allergic encephalomyelitis

MS:

Multiple sclerosis

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Acknowledgments

The authors thank our fellow collaborators in the Aging Program Project (NIA AG00001) particularly Drs. Peters, Rosene, Moss, Leubke, Hollander, Duce, and Chen.

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  1. Departments of Biochemistry and Medicine, Boston University School of Medicine, 715 Albany Street, K620, Boston, MA, 02118, USA

    Jason D. Hinman & Carmela R. Abraham

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  1. Jason D. Hinman
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Correspondence to Carmela R. Abraham.

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Special issue in honor of Naren Banik.

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Hinman, J.D., Abraham, C.R. What’s Behind the Decline? The Role of White Matter in Brain Aging. Neurochem Res 32, 2023–2031 (2007). https://doi.org/10.1007/s11064-007-9341-x

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